A. A. Aljabali, A, A. Bakshi, H, L. Hakkim, F, Haggag, YA, M. Al-Batanyeh, K, S. Al Zoubi, M, Al-Trad, B, M. Nasef, M, Satija, S, Mehta, M, Pabreja, K, Mishra, V, Khan, M, Abobaker, S, M. Azzouz, I, Dureja, H, M. Pabari, R, Ali K. Dardouri, A, Kesharwani, P, Gupta, G, Dhar Shukla, S, Prasher, P, B. Charbe, N, Negi, P, N. Kapoor, D, Chellappan, DK, Webba da Silva, M, Thompson, P, Dua, K, McCarron, P & M. Tambuwala, M 2020, 'Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α', Cancers, vol. 12, no. 1, pp. 113-113.
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Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC–BSA nanoparticles (NPs). These PIC–BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC–BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC–BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC–BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC–BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.
Aggarwal, T, Wadhwa, R, Gupta, R, Paudel, KR, Collet, T, Chellappan, DK, Gupta, G, Perumalsamy, H, Mehta, M, Satija, S, Hansbro, PM, Dua, K & Maurya, PK 2020, 'MicroRNAs as Biomarker for Breast Cancer', Endocrine, Metabolic & Immune Disorders - Drug Targets, vol. 20, no. 10, pp. 1597-1610.
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Regardless of advances in detection and treatment, breast cancer affects about 1.5 millionwomen all over the world. Since the last decade, genome-wide association studies (GWAS) have beenextensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosisand therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation ofkey cellular processes such as cell multiplication, differentiation, and death. They cause a disturbancein the cell physiology by interfering directly with the translation and stability of a targeted gene transcript.MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate targetgene expression and protein levels that affect several human diseases and are suggested as the novelmarkers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not onlyassociated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis orprognosis. These are explained in detail in the following review. This review will also provide an impetusto study the role of microRNAs in breast cancer.
Akshayaa, L 2020, 'Molecular docking analysis of HER-2 inhibitor from the ZINC database as anticancer agent', Bioinformation, vol. 16, no. 11, pp. 878-881.
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Design and development of effective anti-virals in combating CoVid-19 is a great challenge worldwide. Known drugs such as chloroquine, lopinavir, favipiravir and remdesivir are used in the management of CoVid - 19. It is known that Ivermectin and remdesivir both are effective against filoviruses, paramyxo viruses. Available data also shows that ivermectin and remedesivir repress the replication of SARS-CoV-2. Thus, we document the potential use of ivermectin and remdesivir in the management of CoVid -19.
Aljabali, AAA, Bakshi, HA, Hakkim, FL, Haggag, YA, Al-Batanyeh, KM, Zoubi, MSA, Al-Trad, B, Nasef, MM, Satija, S, Mehta, M, Pabreja, K, Mishra, V, Khan, M, Abobaker, S, Azzouz, IM, Dureja, H, Pabari, RM, Dardouri, AAK, Kesharwani, P, Gupta, G, Dhar Shukla, S, Prasher, P, Charbe, NB, Negi, P, Kapoor, DN, Chellappan, DK, Webba da Silva, M, Thompson, P, Dua, K, McCarron, P & Tambuwala, MM 2020, 'Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113', Cancers, vol. 12, no. 12, pp. 3587-3587.
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The authors wish to make the following corrections to this paper [...]
Aljabali, AAA, Bakshi, HA, Satija, S, Metha, M, Prasher, P, Ennab, RM, Chellappan, DK, Gupta, G, Negi, P, Goyal, R, Sharma, A, Mishra, V, Dureja, H, Dua, K & Tambuwala, MM 2020, 'COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development', Pharmaceutical Nanotechnology, vol. 8, no. 4, pp. 323-353.
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Objectives:The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.Methods:Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.Results:In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.Lay Summary:An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers...
Altamish, M, Dahiya, R, Singh, AK, Mishra, A, Aljabali, AAA, Satija, S, Mehta, M, Dureja, H, Prasher, P, Negi, P, Kapoor, DN, Goyal, R, Tambuwala, MM, Chellappan, DK, Dua, K & Gupta, G 2020, 'Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome', Critical Reviews in Eukaryotic Gene Expression, vol. 30, no. 3, pp. 245-252.
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Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.
Altamish, M, Samuel, VP, Dahiya, R, Singh, Y, Deb, PK, Bakshi, HA, Tambuwala, MM, Chellappan, DK, Collet, T, Dua, K & Gupta, G 2020, 'Molecular signaling of G‐protein‐coupled receptor in chronic heart failure and associated complications', Drug Development Research, vol. 81, no. 1, pp. 23-31.
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AbstractThe well‐known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1‐, β2‐, and β3‐adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin‐converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1‐7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G‐protein‐coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G‐protein‐mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
Amatya, E, Fois, R, Williams, KA & Pont, LG 2020, 'Potential for Detection of Safety Signals for Over-the-Counter Medicines Using National ADR Spontaneous Reporting Data: The Example of OTC NSAID-Associated Gastrointestinal Bleeding', Pharmacy, vol. 8, no. 3, pp. 174-174.
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One post-marketing surveillance challenge for many regulatory authorities is access to information regarding the safety of over-the-counter (OTC) medicines. National spontaneous adverse drug reaction (ADR) report data represent a rich potential data source for the detection of safety signals associated with OTC medicines, yet little is known regarding the possibility of detecting safety signals for OTC medicines within these datasets. The aim of this study was to evaluate the potential for detecting safety signals for OTC medicines in National ADR spontaneous reporting data, using OTC non-steroidal anti-inflammatory drugs (NSAIDs) and gastrointestinal bleeding as an example. Data from the Australian Adverse Drug Reactions System (ADRS) dataset (1971–2008) and the Canadian Vigilance Adverse Reaction Online Database (VAROD) (1965–2013) were used to explore the feasibility of using spontaneous reporting data, exploring the association between gastrointestinal bleeding and the use of OTC NSAIDs. Safety signals were examined using disproportionality analyses and reporting odds ratios calculated. After adjusting for age, gender, medications known to increase the risk of bleeding, and medications used for the management of conditions associated with an increased risk of bleeding, a two-fold increase in the risk of gastrointestinal (GI) bleeding with OTC NSAID was observed within each dataset. This study demonstrates that spontaneous ADR reporting data can be used in pharmacovigilance to monitor the safety of OTC medicines.
Amawi, H, Abu Deiab, GI, A Aljabali, AA, Dua, K & Tambuwala, MM 2020, 'COVID-19 Pandemic: an Overview of epidemiology, pathogenesis, Diagnostics and Potential Vaccines and Therapeutics', Therapeutic Delivery, vol. 11, no. 4, pp. 245-268.
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At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.
Bakshi, H, Zoubi, M, Faruck, H, Aljabali, A, Rabi, F, Hafiz, A, Al-Batanyeh, K, Al-Trad, B, Ansari, P, Nasef, M, Charbe, N, Satija, S, Mehta, M, Mishra, V, Gupta, G, Abobaker, S, Negi, P, Azzouz, I, Dardouri, A, Dureja, H, Prasher, P, Chellappan, D, Dua, K, Webba da Silva, M, Tanani, M, McCarron, P & Tambuwala, M 2020, 'Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage', Nutrients, vol. 12, no. 6, pp. 1901-1901.
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Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
Balusamy, SR, Veerappan, K, Ranjan, A, Kim, Y-J, Chellappan, DK, Dua, K, Lee, J & Perumalsamy, H 2020, 'Phyllanthus emblica fruit extract attenuates lipid metabolism in 3T3-L1 adipocytes via activating apoptosis mediated cell death', Phytomedicine, vol. 66, pp. 153129-153129.
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© 2019 Elsevier GmbH Background: Phyllanthus emblica L. (Indian gooseberry) is widely used in the Ayurveda for thousands of years to treat health complications including disorders of the immune system, diabetes, and obesity. Purpose: For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis. Methods: The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively. Results: Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we ...
Benson, H, Lucas, C & Williams, KA 2020, 'Establishing consensus for general practice pharmacist education: A Delphi study', Currents in Pharmacy Teaching and Learning, vol. 12, no. 1, pp. 8-13.
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INTRODUCTION:An evolving area of pharmacist professional practice is performing as team members in general practice teams. To date, there is a paucity of literature to guide schools and colleges of pharmacy regarding the educational needs of pharmacists training for this area of practice. METHODS:This study employed a three-round e-Delphi method with the aim of establishing a consensus position on educational needs of pharmacists intending to work in the general practice setting. Educators from all Australian universities with a pharmacy school were invited to participate as part of the expert panel. Delphi panellists completed two e-survey rounds. A panel videoconference was then completed with results of the discussion confirmed in a final third e-survey. This study defined a proportion of experts rating agree or strongly agree at ≥75% to determine consensus and disagree or strongly disagree at ≥75% to determine non-consensus. RESULTS:Ten of the 18 invited panellists agreed to participate in the study and completed both survey rounds; nine panellists completed the third-round survey. Twenty-six general practice pharmacist activities were identified as educational needs. Seventeen general practice pharmacist activities required no additional training. Five general practice pharmacist activities did not reach consensus. CONCLUSIONS:This study is one of the first investigations of educational needs of pharmacists wishing to practice in the general practice setting. The panel differentiated between activities that could be performed by less experienced pharmacists operating at a general level and those that would require further training.
Benson, H, Lucas, C, Woulfe, J & Williams, KA 2020, 'Training for team-based care: Development of a continuing education curriculum for General Practice pharmacists in Australia', Pharmacy Education, vol. 20, no. 1, pp. 198-203.
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Background: The integration of pharmacists into primary care and general practice teams is expanding. Equipping pharmacists with the skills and knowledge to perform as part of a primary care team will facilitate this expanded scope of practice.Aim: This paper describes the rationale and approach for the development of a competency aligned curriculum of a postgraduate pharmacist education programme in Australia.Methods: The authors describe an evidence-based approach to curriculum development including establishing an educational programme advisory committee, consultation with an expert panel of pharmacy practice educators, and mapping of curriculum to both learning outcomes and competency standards.Conclusions: The curriculum design approach ensures the programme is designed to provide pharmacists with the skills, training and knowledge required to perform the General Practice pharmacist role. The education programme is due to be piloted in 2020, followed by an evaluation to allow further adjustment and improvement of the course design.
Carbajal de Lara, JA, Cantalapiedra Fernández, F, Eguilleor Villena, A, Gutiérrez Ríos, P, Amador Fernández, N & Molinero, A 2020, 'Perfil de las solicitudes de antibióticos en farmacia comunitaria con receta privada y prescripción irregular', Medicina de Familia. SEMERGEN, vol. 46, no. 3, pp. 194-201.
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Chan, Y, Ng, SW, Mehta, M, Anand, K, Kumar Singh, S, Gupta, G, Chellappan, DK & Dua, K 2020, 'Advanced drug delivery systems can assist in managing influenza virus infection: A hypothesis', Medical Hypotheses, vol. 144, pp. 110298-110298.
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© 2020 Elsevier Ltd Outbreaks of influenza infections in the past have severely impacted global health and socioeconomic growth. Antivirals and vaccines are remarkable medical innovations that have been successful in reducing the rates of morbidity and mortality from this disease. However, the relentless emergence of drug resistance has led to a worrisome increase in the trend of influenza outbreaks, characterized by worsened clinical outcomes as well as increased economic burden. This has prompted the need for breakthrough innovations that can effectively manage influenza outbreaks. This article provides an insight into a novel hypothesis that describes how the integration of nanomedicine, with the development of drugs and vaccines can potentially enhance body immune response and the efficacies of anti-viral therapeutics to combat influenza infections.
Chan, Y, Ng, SW, Xin Tan, JZ, Gupta, G, Tambuwala, MM, Bakshi, HA, Dureja, H, Dua, K, Ishaq, M, Caruso, V & Chellappan, DK 2020, 'Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms', Chemico-Biological Interactions, vol. 315, pp. 108911-108911.
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Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
Charbe, NB, Amnerkar, ND, Ramesh, B, Tambuwala, MM, Bakshi, HA, Aljabali, AAA, Khadse, SC, Satheeshkumar, R, Satija, S, Metha, M, Chellappan, DK, Shrivastava, G, Gupta, G, Negi, P, Dua, K & Zacconi, FC 2020, 'Small interfering RNA for cancer treatment: overcoming hurdles in delivery', Acta Pharmaceutica Sinica B, vol. 10, no. 11, pp. 2075-2109.
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© 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
Chellappan, DK, Yee, LW, Xuan, KY, Kunalan, K, Rou, LC, Jean, LS, Ying, LY, Wie, LX, Chellian, J, Mehta, M, Satija, S, Singh, SK, Gulati, M, Dureja, H, Da Silva, MW, Tambuwala, MM, Gupta, G, Paudel, KR, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases', Drug Development Research, vol. 81, no. 4, pp. 419-436.
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AbstractNeutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil‐based therapy.
Chin, LH, Hon, CM, Chellappan, DK, Chellian, J, Madheswaran, T, Zeeshan, F, Awasthi, R, Aljabali, AAA, Tambuwala, MM, Dureja, H, Negi, P, Kapoor, DN, Goyal, R, Paudel, KR, Satija, S, Gupta, G, Hsu, A, Wark, P, Mehta, M, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Molecular mechanisms of action of naringenin in chronic airway diseases', European Journal of Pharmacology, vol. 879, pp. 173139-173139.
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Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.
Dineen-Griffin, S, Benrimoj, SI, Rogers, K, Williams, KA & Garcia-Cardenas, V 2020, 'Cluster randomised controlled trial evaluating the clinical and humanistic impact of a pharmacist-led minor ailment service', BMJ Quality & Safety, vol. 29, no. 11, pp. 921-931.
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BackgroundCommunity pharmacists are well positioned to support patients’ minor ailments. The objective was to evaluate the clinical and humanistic impact of a minor ailment service (MAS) in community pharmacy compared with usual pharmacist care (UC).MethodsA cluster randomised controlled trial was conducted. Intervention patients received MAS, which included a consultation with the pharmacist. MAS pharmacists were trained in clinical pathways and communication systems mutually agreed with general practitioners and received monthly support. Control patients received UC. All patients were followed up by telephone at 14 days. Clinical and humanistic impact were defined by primary (appropriate referral rate and appropriate non-prescription medicine rate) and secondary outcomes (clinical product-based intervention rate, referral adherence, symptom resolution, reconsultation and EuroQol EQ-5D visual analogue scale (VAS)).ResultsPatients (n=894) were recruited from 30 pharmacies and 82% (n=732) responded to follow-up. Patients receiving MAS were 1.5 times more likely to receive an appropriate referral (relative rate (RR)=1.51; 95% CI 1.07 to 2.11; p=0.018) and were five times more likely to adhere to referral, compared with UC (RR=5.08; 95%CI 2.02 to 12.79; p=0.001). MAS patients (94%) achieved symptom resolution or relief at follow-up, while this was 88% with UC (RR=1.06; 95% CI 1 to 1.13; p=0.035). MAS pharmacists were 1.2 times more likely to recommend an appropriate medicine (RR 1.20, 95% CI 1.1 to 1.3; p=0.000) and were 2.6 times more likely to perform a clinical product-based intervention (RR=2.62, 95% CI 1.28 to 5.38; p=0.009), compared with UC. MAS patients had a greater mean difference in VAS at follow-up (4.08; 95% CI 1.23 to 6.87; p=0.004). No difference in reconsultation was observe...
Dineen-Griffin, S, Vargas, C, Williams, KA, Benrimoj, SI & Garcia-Cardenas, V 2020, 'Cost utility of a pharmacist-led minor ailment service compared with usual pharmacist care', Cost Effectiveness and Resource Allocation, vol. 18, no. 1.
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AbstractBackgroundA cluster randomised controlled trial (cRCT) performed from July 2018 to March 2019 demonstrated the clinical impact of a community pharmacist delivered minor ailment service (MAS) compared with usual pharmacist care (UC). MAS consisted of a technology-based face-to-face consultation delivered by trained community pharmacists. The consultation was guided by clinical pathways for assessment and management, and communication systems, collaboratively agreed with general practitioners. MAS pharmacists were trained and provided monthly practice support by a practice change facilitator. The objective of this study was to assess the cost utility of MAS, compared to UC.MethodsParticipants recruited were adult patients with symptoms suggestive of a minor ailment condition, from community pharmacies located in Western Sydney. Patients received MAS (intervention) or UC (control) and were followed-up by telephone 14-days following consultation with the pharmacist. A cost utility analysis was conducted alongside the cRCT. Transition probabilities and costs were directly derived from cRCT study data. Utility values were not available from the cRCT, hence we relied on utility values reported in the published literature which were used to calculate quality adjusted life years (QALYs), using the area under the curve method. A decision tree model was used to capture the decision problem, considering a societal perspective and a 14-day time horizon. Deterministic and probabilistic sensitivity analyses assessed robustness and uncertainty of results, respectively.ResultsPatients (n = 894) were recruited from 30 pharmacies and 82% (n = 732) responded to follow-up. On average, MAS was more costly but also more effective (in terms of symptom resolution and QALY gains) ...
Elliott, RA, Chan, A, Godbole, G, Hendrix, I, Pont, LG, Sfetcopoulos, D, Woodward, J & Munro, C 2020, 'Standard of practice in geriatric medicine for pharmacy services', Journal of Pharmacy Practice and Research, vol. 50, no. 1, pp. 82-97.
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Gandhi, H, Rathore, C, Dua, K, Vihal, S, Tambuwala, MM & Negi, P 2020, 'Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis', Drug Development and Industrial Pharmacy, vol. 46, no. 3, pp. 365-375.
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Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES.
Groen, A, Lucas, C, Benson, H, Alsubaie, M & Boyd, MJ 2020, 'A systematic review of postgraduate training programmes directed at pharmacists entering primary care', Pharmacy Education, vol. 20, pp. 313-323.
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This systematic review explores the international postgraduate education and training programmes designed to provide or develop knowledge or skills focused on enabling pharmacists to work in a general practice setting. Four thousand, eight hundred and seventy-one (4,871) articles were identified from database searches of SCOPUS, EMBASE, Medline, CINAHL, IPA, Web of Science and ERIC. After removal of duplicates and article screening, seven articles were included. Educational content, setting, contact time and methods of assessment varied across all studies. There is paucity of published literature relating to the development and evaluation of education programmes directed at pharmacists entering into general practice. A combination of work and classroom-based education provided by general practitioners and pharmacists already working in primary care is deemed most beneficial coupled with systematic debriefing sessions at the completion of training courses. The findings suggest future training should focus on specific disease states.
Gupta, G, Dahiya, R, Singh, Y, Mishra, A, Verma, A, Gothwal, SK, Aljabali, AAA, Dureja, H, Prasher, P, Negi, P, Kapoor, DN, Goyal, R, Tambuwala, MM, Chellappan, DK & Dua, K 2020, 'Monotherapy of RAAS blockers and mobilization of aldosterone: A mechanistic perspective study in kidney disease', Chemico-Biological Interactions, vol. 317, pp. 108975-108975.
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In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.
Gupta, G, Singh, Y, Tiwari, J, Raizaday, A, Alharbi, KS, Al‐Abbasi, FA, Kazmi, I, Satija, S, Tambuwala, MM, Devkota, HP, Krishnan, A, Chellappan, DK & Dua, K 2020, 'Beta‐catenin non‐canonical pathway: A potential target for inflammatory and hyperproliferative state via expression of transglutaminase 2 in psoriatic skin keratinocyte', Dermatologic Therapy, vol. 33, no. 6, p. e14209.
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Psoriasis is a chronic, local as well as a systemic, inflammatory skin condition. Psoriasis influences the quality of life up to 3.8% of the population and occurs often between 15 and 30 years of age. Specific causes are linked to psoriasis, including the interleukin IL-23/IL-17 Axis, human antigen leucocyte (HLA), and tumor necrosis factor-α (TNF-α). Secukinumab is a monoclonal antibody that specifically binds and neutralizes IL-17A required in the treatment of Psoriasis. The signaling pathways of Wnt govern multiple functions of cell-like fate specification, proliferation, polarity, migration, differentiation with their signaling controlled rigorously, given that dysregulation caused by various stimuli, can lead to alterations in cell proliferation, apoptosis, and human inflammatory disease. Current data has supported non-canonical Wnt signaling pathways in psoriasis development, particularly Wnt5a activated signaling cascades. These interconnected factors are significant in interactions between immune cells, keratinocytes, and inflammatory factors due to a higher degree of transglutaminase 2, mediated by activation of the keratinocyte hyperproliferation of the psoriatic patient's epidermis. This study discusses the pathology of Wnt5a signaling and its involvement in the epidermal inflammatory effects of psoriasis with other related pathways.
Jackson, K 2020, 'Cytotoxic potentials of silibinin assisted silver nanoparticles on human colorectal HT-29 cancer cells', Bioinformation, vol. 16, no. 11, pp. 817-827.
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It is of interest to study the cytotoxicity of silibinin assisted silver nanoparticles in human colorectal (HT-29) cancer cells. Silver nanoparticles were synthesized using silibinin as a reducing agent. The synthesized silibinin assisted silver nanoparticles (SSNPs) were characterized and analyzed using a transmission electron microscope and spectrophotometer. The SSNPs synthesized in this study are spherical and their size ranges from 10 to 80 nm. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/mL) of SSNPs and cytotoxicity was evaluated. The apoptosis was using flow cytometry. p53 protein expression using western blot. SSNPs are induced a decrease in viability and increased concentration-dependent cytotoxicity in HT-29 cells. SSNPs treatment also caused apoptosis-related morphological changes. SSNPs treatments at 8 and 16 ng/ml showed a prominent apoptotic change i.e., 70.3% and 83.6% respectively, and decreased viability of HT-29 cells 20% and 11.2% respectively as compared to control cells. SSNPs treatments induced p53 expression in HT-29 cells. Data shows that SSNPs have the potential to induce apoptosis in colorectal cancer cells. This provides insights for the further evaluation of SSNPs in fighting colon cancer.
Jayanthi, M, Gokulanathan, A, Haribalan, P, Ashakiran, K, Dinesh Kumar, C, Kamal, D, Girija, S & Sri Renukadevi, B 2020, 'Plumbagin from two Plumbago species inhibits the growth of stomach and breast cancer cell lines', Industrial Crops and Products, vol. 146, pp. 112147-112147.
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© 2020 Elsevier B.V. Plumbagin is a potent natural molecule that is found in several plants, especially in the genus of Plumbago. For centuries, plants containing this substance have been used therapeutically for various ailments according to the Indian traditional system of medicine. The aims of this study were, firstly, to compare the effectiveness of two different extraction methods for the isolation of plumbagin and, secondly, to compare the anti-proliferative effects of plumbagin in both field grown and in vitro grown plants of Plumbago indica L. and Plumbago zeylanica L. Plumbagin was quantified from different parts, viz from the leaf, stem and root of both field and in vitro grown plants of Plumbago indica. Plumbagin was isolated using the serial maceration extraction method using methanol as solvent. Anti-proliferative activity of selected extracts was examined in both stomach cancer cell lines (AGS) and breast cancer cell lines (MDA-MB-231). Quantification of plumbagin was performed by reverse phase high performance liquid chromatography (HPLC). The leaves, stem and roots of the in vitro grown Plumbago indica yielded 70.98 mg g−1, 22.45 mg g−1and 342.15 mg g−1of content, respectively. This was higher when compared to the field grown parts (28.87 mg g−1, 11.54 mg g-1 and 2687 mg g−1). We have demonstrated that different extraction methods have varied yield of plumbagin. The isolated compound was then tested for its anti-proliferative activity. Also, we have confirmed apoptotic medicated cell death by nucleus staining to detect cell death by the treatment of different type of extract of both Plumbago indica L. and Plumbago zeylanica L.
Jha, NK, Sharma, A, Jha, SK, Ojha, S, Chellappan, DK, Gupta, G, Kesari, KK, Bhardwaj, S, Shukla, SD, Tambuwala, MM, Ruokolainen, J, Dua, K & Singh, SK 2020, 'Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies', Open Biology, vol. 10, no. 12, pp. 200286-200286.
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Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood–brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.
Jose, ZM, Maria Isabel, VM, Maria, FR, Noelia, AF & Fernando, MM 2020, 'Training in Professional Pharmacy Services through Educational Videos', Indian Journal of Pharmaceutical Education and Research, vol. 54, no. 4, pp. 881-887.
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Kaur, G, Singh, SK, Kumar, R, Kumar, B, Kumari, Y, Gulati, M, Pandey, NK, Gowthamarajan, K, Ghosh, D, Clarisse, A, Wadhwa, S, Mehta, M, Satija, S, Dua, K, Dureja, H, Gupta, S, Singh, PK, Kapoor, B, Chitranshi, N, Kumar, A & Porwal, O 2020, 'Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis', Journal of Drug Delivery Science and Technology, vol. 60, pp. 101980-101980.
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© 2020 Elsevier B.V. The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and −16.3 ± 1.54 mV and AgNPs loaded with MES (AgNPs-MES) was 101 ± 9 nm and −14.27 ± 2.16 mV. The dissolution study revealed about 54% drug release after 5 h indicating release of drug at the colonic site. The in vivo study was carried out on acetic acid induced ulcerative colitis rats and efficacy of treatment was assessed through evaluation of disease activity index and level of antioxidants as well as tumor necrosis factor-α after 7th and 14th day of induction of colitis. Histopathological evaluation of colonic tissue was also carried out. The results revealed that AgNPs-MES (high dose) provided better therapeutic efficacy for the treatment of UC as compared to its low dose, MES alone, MES-MAP, AgNPs alone and MAP alone. It was concluded that MAP based AgNPs loaded with MES were successfully formulated and found to be effective in treating ulcerative colitis.
Khatak, S, Mehta, M, Awasthi, R, Paudel, KR, Singh, SK, Gulati, M, Hansbro, NG, Hansbro, PM, Dua, K & Dureja, H 2020, 'Solid lipid nanoparticles containing anti-tubercular drugs attenuate the Mycobacterium marinum infection', Tuberculosis, vol. 125, pp. 102008-102008.
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The present study aimed to formulate anti-tubercular drugs (Rifampicin, Isoniazid and Pyrazinamide) loaded solid lipid nanoparticles (ATDs-SLNs) using microemulsion technique for oral administration. Central composite designed (CCD) was applied to study the effect of stearic acid (X1), Compritol® 888 ATO (X2) and equal ratio of poloxamer 188: sodium taurocholate (% w/w) (X3) on particle size, zeta potential and entrapment efficiency. The optimised formulation (SLN8) was found to be spherical in shape with mean particle size 187.9 ± 10.73 nm and zeta potential -47.4 mV. The maximum percentage entrapment of RIF, INH and PYZ in the optimised formulation was found to be 86.40 ± 0.274, 83.84 ± 0.269 and 81.43 ± 0.576, respectively. The in-vitro drug release study demonstrated that the release of drug from SLNs was slow in comparison to marketed formulation and pure ATDs. Cytotoxicity of the ATDs-SLNs was studied on murine macrophage cell line (RAW 264.7) using modified MTT assay demonstrated two folds growth inhibition of M. marinum as compared to standard antitubercular drugs. Overall, the developed SLNs may be considered as a promising anti-mycobacterial nano-drug, providing a new direction to the tuberculosis clinics.
Kou, J, Xin, TY, McCarron, P, Gupta, G, Dureja, H, Satija, S, Mehta, M, Bakshi, HA, Tambuwala, MM, Collet, T, Dua, K & Chellappan, DK 2020, 'Going Beyond Antibiotics: Natural Plant Extracts as an Emergent Strategy to Combat Biofilm-Associated Infections', Journal of Environmental Pathology, Toxicology and Oncology, vol. 39, no. 2, pp. 125-136.
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Biofilms are a collective of multiple types of bacteria that develop on a variety of surfaces. Biofilm development results in heightened resistance to antibiotics. Quorum sensing plays an important role in biofilm development as it is one of the common communication mechanisms within cells, which balances and stabilizes the environment, when the amount of bacteria increases. Because of the important implications of the roles biofilms play in infectious diseases, it is crucial to investigate natural antibacterial agents that are able to regulate biofilm formation and development. Various studies have suggested that natural plant products have the potential to suppress bacterial growth and exhibit chemopreventive traits in the modulation of biofilm development. In this review, we discuss and collate potential antibiofilm drugs and biological molecules from natural sources, along with their underlying mechanisms of action. In addition, we also discuss the antibiofilm drugs that are currently under clinical trials and highlight their potential future uses.
Kumar, M, Nishad, DK, Kumar, A, Bhatnagar, A, Karwasra, R, Khanna, K, S, K, Sharma, D, Dua, K, Mudaliyar, V & Sharma, N 2020, 'Enhancement in brain uptake of vitamin D3 nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models', Journal of Microencapsulation, vol. 37, no. 7, pp. 492-501.
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Aim
For the treatment of cerebral ischaemia, vitamin-D
3 loaded nanoemulsions were developed.
Method
Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various
in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model.
Result
Vitamin D
3-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of
99mTc-vitamin D
3-nanoemulsion through nasal route compared to IV administered
99mTc-vitamin D
3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D
3-nanoemulsion.
Conclusion
This work demonstrated better permeation, deposition, and efficacy of vitaminD
3-nanoemulsion through the intranasal route.
Madan, JR, Ansari, IN, Dua, K & Awasthi, R 2020, 'Formulation and In Vitro Evaluation of Casein Nanoparticles as Carrier for Celecoxib', Advanced Pharmaceutical Bulletin, vol. 10, no. 3, pp. 408-417.
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Purpose : The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). Methods: The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further, in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. Results: The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. The in vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time poin...
Madan, JR, Khobaragade, S, Dua, K & Awasthi, R 2020, 'Formulation, optimization, and in vitro evaluation of nanostructured lipid carriers for topical delivery of Apremilast', Dermatologic Therapy, vol. 33, no. 3.
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This work was aimed to formulate topical Apremilast (APM)-loaded nanostructured lipid carriers (NLCs) for the management of psoriasis. NLCs were prepared by a cold homogenization technique using Compritol 888ATO, oleic acid, Tween 80 and Span 20, and Transcutol P as a solid lipid, liquid lipid, surfactant mixture, and penetration enhancer, respectively. Carbopol 940 was used to convert NLC dispersion into NLC-based hydrogel to improve its viscosity for topical administration. The optimized formulation was characterized for size, polydispersity index (PDI), zeta potential (ZP), percentage of entrapment efficiency (%EE), and surface morphology. Furthermore, viscosity, spreadability, stability, in vitro drug diffusion, ex vivo skin permeation, and skin deposition studies were carried out. APM-loaded NLCs showed a narrow PDI (0.339) with a particle size of 758 nm, a %EE of 85.5%, and a ZP of -33.3 mV. Scanning electron microscopy confirmed spherical shape of NLCs. in vitro drug diffusion and ex vivo skin permeation results showed low drug diffusion, sustained drug release, and 60.1% skin deposition. The present study confirms the potential of the nanostructured lipid form of poorly water-soluble drugs for topical application and increased drug deposition in the skin.
Makeham, M, Pont, L, Verdult, C, Hardie, R-A, Raban, MZ, Mitchell, R, Purdy, H, Teichert, M, Ingersoll, A & Westbrook, JI 2020, 'The General Practice and Residential Aged Care Facility Concordance of Medication (GRACEMED) study', International Journal of Medical Informatics, vol. 143, pp. 104264-104264.
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BACKGROUND: The lack of interoperable IT systems between residential aged care facilities (RACF) and general practitioners (GP) in primary care settings in Australia introduces the potential for medication discrepancies and other medication errors. The aim of the GRACEMED study is to determine the extent and potential severity of medication discrepancies between general practice and RACFs, and identify factors associated with medication discrepancies. METHODS: A cross sectional study of medication discrepancies between RACF medication orders and GP medication lists was conducted in the Sydney North Health Network, Australia. A random sample of RACF residents was included from practice lists provided by the general practices. RACF medication orders and GP medication lists for the included residents were compared, and medication discrepancies between the two sources were identified and characterised in terms of discrepancy type, potential for harm and associated factors. RESULTS: 31 GPs and 203 residents were included in the study. A total of 1777 discrepancies were identified giving an overall discrepancy rate of 72.6 discrepancies for every 100 medications. Omissions were the most common discrepancy type (35.2%,) followed by dose discrepancies (34.4%) and additions (30.4%). 48.5% of residents had a discrepancy with the potential to result in moderate harm and 9.8% had a discrepancy with the potential for severe harm. Number of medications prescribed was the only factor associated with medication discrepancies. CONCLUSION: Increased use of systems that allow information sharing and improved interoperability of clinical information is urgently needed to address medication safety issues experienced by RACF residents.
Malyla, V, Paudel, KR, Shukla, SD, Donovan, C, Wadhwa, R, Pickles, S, Chimankar, V, Sahu, P, Bielefeldt-Ohmann, H, Bebawy, M, Hansbro, PM & Dua, K 2020, 'Recent Advances in Experimental Animal Models of Lung Cancer', Future Medicinal Chemistry, vol. 12, no. 7, pp. 567-570.
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Manandhar, B, Cochran, BJ & Rye, K 2020, 'Role of High‐Density Lipoproteins in Cholesterol Homeostasis and Glycemic Control', Journal of the American Heart Association, vol. 9, no. 1.
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Manandhar, B, Kim, HJ & Rhyu, DY 2020, 'Caulerpa okamurae extract attenuates inflammatory interaction, regulates glucose metabolism and increases insulin sensitivity in 3T3-L1 adipocytes and RAW 264.7 macrophages', Journal of Integrative Medicine, vol. 18, no. 3, pp. 253-264.
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Mehta, M, Chellappan, DK, Wich, PR, Hansbro, NG, Hansbro, PM & Dua, K 2020, 'miRNA Nanotherapeutics: Potential and Challenges in Respiratory Disorders', Future Medicinal Chemistry, vol. 12, no. 11, pp. 987-990.
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Mehta, M, Dhanjal, DS, Paudel, KR, Singh, B, Gupta, G, Rajeshkumar, S, Thangavelu, L, Tambuwala, MM, Bakshi, HA, Chellappan, DK, Pandey, P, Dureja, H, Charbe, NB, Singh, SK, Shukla, SD, Nammi, S, Aljabali, AA, Wich, PR, Hansbro, PM, Satija, S & Dua, K 2020, 'Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update', Inflammopharmacology, vol. 28, no. 4, pp. 795-817.
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Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients.
Mehta, M, Dhanjal, DS, Satija, S, Wadhwa, R, Paudel, KR, Chellappan, DK, Mohammad, S, Haghi, M, Hansbro, PM & Dua, K 2020, 'Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems', Current Pharmaceutical Design, vol. 26, no. 42, pp. 5380-5392.
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Cell Signaling pathways form an integral part of our existence that allows the cells to comprehend astimulus and respond back. Such reactions to external cues from the environment are required and are essential toregulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed inthese signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the thirdleading cause of morbidity worldwide. According to the current statistics, over 339 million people are asthmatic,65 million are suffering from COPD, 2.3 million are lung cancer patients and 10 million are tuberculosis patients.This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and the nation's annualhealth expenditure. Hence, a better understanding of the processes governing these cellular pathways will enableus to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend thesynergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to exploreand develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratorydiseases and further provides an in-depth discussion on the various cell signaling pathways that are involvedin the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts aboutadvanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimizethe current challenges faced by researchers and formulation scientists.
Mehta, M, Paudel, KR, Shukla, SD, Shastri, MD, Singh, SK, Gulati, M, Dureja, H, Gupta, G, Satija, S, Hansbro, PM, Chellappan, DK & Dua, K 2020, 'Interferon therapy for preventing COPD exacerbations.', EXCLI J, vol. 19, pp. 1477-1480.
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Mehta, M, Prasher, P, Sharma, M, Shastri, MD, Khurana, N, Vyas, M, Dureja, H, Gupta, G, Anand, K, Satija, S, Chellappan, DK & Dua, K 2020, 'Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis', Medical Hypotheses, vol. 144, pp. 110254-110254.
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© 2020 Elsevier Ltd The highly contagious coronavirus, which had already affected more than 2 million people in 210 countries, triggered a colossal economic crisis consequently resulting from measures adopted by various goverments to limit transmission. This has placed the lives of many people infected worldwide at great risk. Currently there are no established or validated treatments for COVID-19, that is approved worldwide. Nanocarriers may offer a wide range of applications that could be developed into risk-free approaches for successful therapeutic strategies that may lead to immunisation against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) which is the primary causative organism that had led to the current COVID-19 pandemic. We address existing as well as emerging therapeutic and prophylactic approaches that may enable us to effectively combat this pandemic, and also may help to identify the key areas where nano-scientists can step in.
Mehta, M, Satija, S, Paudel, KR, Liu, G, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Incipient Need of Targeting Airway Remodeling Using Advanced Drug Delivery in Chronic Respiratory Diseases', Future Medicinal Chemistry, vol. 12, no. 10, pp. 873-875.
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Molinero, A, Carbajal de Lara, JA, Cantalapiedra Fernández, F, Eguilleor Villena, A, Gutiérrez Ríos, P & Amador-Fernández, N 2020, 'Demanda de antibióticos sin prescripción en la farmacia comunitaria. Descripción de la intervención del farmacéutico', Medicina de Familia. SEMERGEN, vol. 46, no. 8, pp. 545-552.
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Ng, PQ, Ling, LSC, Chellian, J, Madheswaran, T, Panneerselvam, J, Kunnath, AP, Gupta, G, Satija, S, Mehta, M, Hansbro, PM, Collet, T, Dua, K & Chellappan, DK 2020, 'Applications of Nanocarriers as Drug Delivery Vehicles for Active Phytoconstituents', Current Pharmaceutical Design, vol. 26, no. 36, pp. 4580-4590.
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Many plant-based bioactive compounds have been serving as the origin of drugs since long ago andmany of them have been proven to have medicinal value against various chronic diseases, including, cancer,arthritis, hepatic diseases, type-2 diabetes and cardiovascular diseases. However, their clinical applications havebeen limited due to their poor water solubility, stability, low bioavailability and extensive transformation due tothe first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery ofbioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and therebyincreasing the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity tohealthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance thedelivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related tobioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.
Pandey, NK, Singh, SK, Gulati, M, Kumar, B, Kapoor, B, Ghosh, D, Kumar, R, Khursheed, R, Awasthi, A, Kuppusamy, G, Wadhwa, S, Satija, S, Dureja, H, Jain, SK, Chellappan, DK, Anand, K, Mehta, M & Dua, K 2020, 'Overcoming the dissolution rate, gastrointestinal permeability and oral bioavailability of glimepiride and simvastatin co-delivered in the form of nanosuspension and solid self-nanoemulsifying drug delivery system: A comparative study', Journal of Drug Delivery Science and Technology, vol. 60, pp. 102083-102083.
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© 2020 Elsevier B.V. Simvastatin (SIM) and glimepiride (GLM) were co-formulated into nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) to improve their dissolution rate and oral bioavailability. Nanosuspension was prepared by liquid anti-solvent precipitation method, involving supersaturation of a solution by mixing the drug solution in an antisolvent. Liquid SNEDDS were prepared by loading drugs into an isotropic mixture of Capmul MCM, Labrafil M1944CS, Tween-80 and Transcutol P. Both formulations were solidified using spray drying. Enhancement in dissolution rate by 6.4 folds and 4.45 folds was observed for GLM and SIM respectively by preparing their nano-formulations. Drugs’ permeability was also enhanced by loading them into nano-formulations. The pharmacokinetic studies were conducted on rats which revealed increase in oral bioavailability by 6.69- and 4.22-folds for GLM and 1.76- and 2.68-folds for SIM respectively for nanosuspension and solid SNEDDS than their unprocessed forms. Both dissolution rate and oral bioavailability of SIM and GLM got significantly improved through S-SNEDDS and nanosuspension. However, performance of nanosuspension was found better than SNEDDS in terms of dissolution rate and oral bioavailability.
Pandey, P, Satija, S, Wadhwa, R, Mehta, M, Purohit, D, Gupta, G, Prasher, P, Chellappan, DK, Awasthi, R, Dureja, H & Dua, K 2020, 'Emerging trends in nanomedicine for topical delivery in skin disorders: Current and translational approaches', Dermatologic Therapy, vol. 33, no. 3.
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Pardhi, DM, Şen Karaman, D, Timonen, J, Wu, W, Zhang, Q, Satija, S, Mehta, M, Charbe, N, McCarron, PA, Tambuwala, MM, Bakshi, HA, Negi, P, Aljabali, AA, Dua, K, Chellappan, DK, Behera, A, Pathak, K, Watharkar, RB, Rautio, J & Rosenholm, JM 2020, 'Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens', International Journal of Pharmaceutics, vol. 586, pp. 119531-119531.
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This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
Paudel, KR, Dharwal, V, Patel, VK, Galvao, I, Wadhwa, R, Malyla, V, Shen, SS, Budden, KF, Hansbro, NG, Vaughan, A, Yang, IA, Kohonen-Corish, MRJ, Bebawy, M, Dua, K & Hansbro, PM 2020, 'Role of Lung Microbiome in Innate Immune Response Associated With Chronic Lung Diseases', Frontiers in Medicine, vol. 7, p. 554.
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Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis, and lung cancer, pose a huge socio-economic burden on society and are one of the leading causes of death worldwide. In the past, culture-dependent techniques could not detect bacteria in the lungs, therefore the lungs were considered a sterile environment. However, the development of culture-independent techniques, particularly 16S rRNA sequencing, allowed for the detection of commensal microbes in the lung and with further investigation, their roles in disease have since emerged. In healthy individuals, the predominant commensal microbes are of phylum Firmicutes and Bacteroidetes, including those of the genera Veillonella and Prevotella. In contrast, pathogenic microbes (Haemophilus, Streptococcus, Klebsiella, Pseudomonas) are often associated with lung diseases. There is growing evidence that microbial metabolites, structural components, and toxins from pathogenic and opportunistic bacteria have the capacity to stimulate both innate and adaptive immune responses, and therefore can contribute to the pathogenesis of lung diseases. Here we review the multiple mechanisms that are altered by pathogenic microbiomes in asthma, COPD, lung cancer, and lung fibrosis. Furthermore, we focus on the recent exciting advancements in therapies that can be used to restore altered microbiomes in the lungs.
Paudel, KR, Wadhwa, R, Mehta, M, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro', Toxicology in Vitro, vol. 68, pp. 104961-104961.
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Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.
Prasher, P, Sharma, M, Aljabali, AAA, Gupta, G, Negi, P, Kapoor, DN, Singh, I, Zacconi, FC, de Jesus Andreoli Pinto, T, da Silva, MW, Bakshi, HA, Chellappan, DK, Tambuwala, MM & Dua, K 2020, 'Hybrid molecules based on 1,3,5‐triazine as potential therapeutics: A focused review', Drug Development Research, vol. 81, no. 7, pp. 837-858.
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AbstractMajority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux‐pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5‐triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5‐triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5‐triazine based hybrid molecules in the development of pharmaceuticals.
Prasher, P, Sharma, M, Mehta, M, Paudel, KR, Satija, S, Chellappan, DK, Dureja, H, Gupta, G, Tambuwala, MM, Negi, P, Wich, PR, Hansbro, NG, Hansbro, PM & Dua, K 2020, 'Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective', Chemico-Biological Interactions, vol. 325, pp. 109125-109125.
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The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.
Prasher, P, Sharma, M, Mudila, H, Gupta, G, Sharma, AK, Kumar, D, Bakshi, HA, Negi, P, Kapoor, DN, Chellappan, DK, Tambuwala, MM & Dua, K 2020, 'Emerging trends in clinical implications of bio-conjugated silver nanoparticles in drug delivery', Colloid and Interface Science Communications, vol. 35, pp. 100244-100244.
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© 2020 Elsevier B.V. From nanopharmaceutics to renewable energy, silver nanoparticles (AgNPs) present innumerable applications in the contemporary era. However, the associated toxicity to the biosystems limits their application. Effective utilization of AgNPs, therefore, requires their surface conjugation with biologically benevolent moieties that enhance the bio-acceptability of silver-based nanosystems, and supplementary functionalities for further extension of their unique applications. The clinical importance of AgNPs was established long ago, but their clinical utilization has been explored only recently with the phenomenon of bio-conjugation. The biomolecule-conjugated AgNPs present operable solutions for tedious clinical complications of the present era, such as multidrug resistance, designing of pharmaceuticals with improved bioavailability, superior drug delivery vehicles and in situ bio imaging of important metabolites that utilize the biomolecule-anchored surface engineered AgNPs. This review epigrammatically discusses some interesting clinical applications of surface conjugated AgNPs with biomolecules such as peptides, nucleic acids, amino acids and antibodies in the current nanopharmaceutical paradigm.
Rajeev Krishnan, S, De Rubis, G, Suen, H, Joshua, D, Lam Kwan, Y & Bebawy, M 2020, 'A liquid biopsy to detect multidrug resistance and disease burden in multiple myeloma', Blood Cancer Journal, vol. 10, no. 3.
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AbstractMultiple myeloma is an incurable cancer of bone marrow plasma cells, with a 5-year survival rate of 43%. Its incidence has increased by 126% since 1990. Treatment typically involves high-dose combination chemotherapy, but therapeutic response and patient survival are unpredictable and highly variable—attributed largely to the development of multidrug resistance (MDR). MDR is the simultaneous cross-resistance to a range of unrelated chemotherapeutic agents and is associated with poor prognosis and survival. Currently, no clinical procedures allow for a direct, continuous monitoring of MDR. We identified circulating large extracellular vesicles (specifically microparticles (MPs)) that can be used to monitor disease burden, disease progression and development of MDR in myeloma. These MPs differ phenotypically in the expression of four protein biomarkers: a plasma-cell marker (CD138), the MDR protein, P-glycoprotein (P-gp), the stem-cell marker (CD34); and phosphatidylserine (PS), an MP marker and mediator of cancer spread. Elevated levels of P-gp+and PS+MPs correlate with disease progression and treatment unresponsiveness. Furthermore, P-gp, PS and CD34 are predominantly expressed in CD138−MPs in advanced disease. In particular, a dual-positive (CD138−P-gp+CD34+) population is elevated in aggressive/unresponsive disease. Our test provides a personalised liquid biopsy with potential to address the unmet clinical need of monitoring MDR and treatment failure in myeloma.
Ramamoorthy, K 2020, 'Anticancer effects and lysosomal acidification in A549 cells by astaxanthin from Haematococcus lacustris', Bioinformation, vol. 16, no. 11, pp. 965-973.
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Astaxanthin (AXN) is known to have health benefits by epidemiological studies. Therefore, it is of interest to assess the effect of AXN (derived from indigenous unicellular green alga Haematococcus lacustris) to modulate cell cycle arrest, lysosomal acidification and eventually apoptosis using in vitro in A549 lung cancer cells. Natural extracts of astaxanthin were obtained by standardized methods as reported earlier and characterized by standard HPLC and MS. Treatment of A549 cells with AXN (purified fraction) showed significant reduction in cell viability (about 50%) as compared to crude extract at 50µM concentration. Thus, we show the anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris for further consideration. Together, our results demonstrated the anticancer potential of AXN from Haematococcus lacustris, which is found to be mediated via its ability to induce cell cycle arrest, lysosomal acidification and apoptotic induction.
Ranpise, HA, Gujar, KN, Pawar, SC, Awasthi, R, Dua, K, Mathure, D & Madan, JR 2020, 'Formulation, Optimization, and Evaluation of Ketoconazole Loaded Nanostructured Lipid Carrier Gel for Topical Delivery', Drug Delivery Letters, vol. 10, no. 1, pp. 61-71.
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Objective:Ketoconazole is used in the treatment of superficial and systemic fungal infections.It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane.The purpose of this work was to formulate ketoconazole loaded nanostructured lipid carriersformulation for skin targeting to minimize the adverse side effects and to prolong release.Methods:The ketoconazole loaded nanostructured lipid carriers were optimized using 32 factorial designto evaluate the effects of process and formulation variables. The nanostructured lipid carriers wereprepared by melt-dispersion ultra-sonication method. The formulations were finally incorporated intopolymeric gels of Carbopol 940 for convenient application. The gels were evaluated comparativelywith commercially available formulations of ketoconazole with respect to ex vivo skin permeation anddeposition study on human cadaver skin.Results:Nanostructured lipid carriers showed average particle size, zeta potential, and percentage entrapmentin the range of 125.8 ± 1.8 to 295.0 ± 3.8 nm, -13.2 ± 1.1 to -30.9 ± 2.2 mV, and 69.47 ± 2.8to 95.49 ± 4.5, respectively. Thermal studies revealed no drug-excipient incompatibility and amorphizationof ketoconazole. Ex vivo study of the gel exhibited prolonged drug release up to 12 h. In vitrodrug deposition study showed that the gel formulation can avoid the systemic uptake, better accumulativeuptake of the drug, and nonirritant to the skin compared to marketed formulation. Optimized formulationexhibited better antifungal activity when compared to ketoconazole loaded gel and marketedcream (Keto ® cream). Histolopathology results indicated no toxic effect on the skin.Conclusion:These results ind...
Rathore, C, Upadhyay, N, Kaundal, R, Dwivedi, RP, Rahatekar, S, John, A, Dua, K, Tambuwala, MM, Jain, S, Chaudari, D & Negi, P 2020, 'Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs', Expert Opinion on Drug Delivery, vol. 17, no. 2, pp. 237-253.
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Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of -0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.
Rawat, S, Singh Dhramshaktu, I, Pathak, S, Kumar Singh, S, Singh, H, Mishra, A, Gilhotra, R, Kumar Chellappan, D, Dua, K & Gupta, G 2020, 'The Impact of COVID-19 Pandemic Infection in Patients Admitted to the Hospital for Reasons Other Than COVID-19 Infection.', Altern Ther Health Med, vol. 26, no. S2, pp. 108-111.
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COVID-19 or SARS CoV-2 is a worldwide public health emergency. The first case of COVID-19 was described in Wuhan, China in December, 2019 and within a short time the infection had spread quickly to the rest of China and then the world. The COVID-19 pandemic has had a huge impact on patients who do not have COVID-19 but other diseases like cancer, diabetes, and many more non-communicable diseases; their care is compromised because of the pandemic. COVID-19 also poses a work-related health risk for healthcare workers who are treating patients with COVID-19, and many have themselves become infected. Healthcare workers involved in diagnosing and treating patients with COVID-19 should be evaluated for stress, anxiety and depression.
Raychaudhuri, R, Pandey, A, Hegde, A, Abdul Fayaz, SM, Chellappan, DK, Dua, K & Mutalik, S 2020, 'Factors affecting the morphology of some organic and inorganic nanostructures for drug delivery: characterization, modifications, and toxicological perspectives', Expert Opinion on Drug Delivery, vol. 17, no. 12, pp. 1737-1765.
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Introduction: In this review, we aim to highlight the impact of various processes and formulation variables influencing the characteristics of certain surfactant-based nanoconstructs for drug delivery. Areas covered: The review includes the discussion on processing parameters for the preparation of nanoconstructs, especially those made up of surfactants. Articles published in last 15 years (437) were reviewed, 381 articles were selected for data review and most appropriate articles (215) were included in article. Effect of variables such as surfactant concentration and type, membrane additives, temperature, and pH-dependent transitions on morphology has been highlighted along with effect of shape on nanoparticle uptake by cells. Various characterization techniques explored for these nanostructures with respect to size, morphology, lamellarity, distribution, etc., and a separate section on polymeric vesicles and the influence of block copolymers, type of block copolymer, control of block length, interaction of multiple block copolymers on the structure of polymersomes and chimeric nanostructures have been discussed. Finally, applications, modification, degradation, and toxicological aspects of these drug delivery systems have been highlighted. Expert opinion: Parameters influencing the morphology of micelles and vesicles can directly or indirectly affect the efficacy of small molecule cellular internalization as well as uptake in the case of biologicals.[Figure: see text].
Satija, S, Mehta, M, Gupta, G, Chellappan, DK & Dua, K 2020, 'Targeting Interleukins in Chronic Airway Diseases Using Advanced Drug Delivery', Future Medicinal Chemistry, vol. 12, no. 20, pp. 1805-1807.
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Satija, S, Mehta, M, Sharma, M, Prasher, P, Gupta, G, Chellappan, DK & Dua, K 2020, 'Vesicular Drug Delivery Systems As Theranostics in COVID-19', Future Medicinal Chemistry, vol. 12, no. 18, pp. 1607-1609.
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Satija, S, Tambuwala, MM, Pabreja, K, Bakshi, HA, Chellappan, DK, Aljabali, AA, Nammi, S, Singh, TG, Dureja, H, Gupta, G, Dua, K, Mehta, M & Garg, M 2020, 'Development of a novel HPTLC fingerprint method for simultaneous estimation of berberine and rutin in medicinal plants and their pharmaceutical preparations followed by its application in antioxidant assay', JPC – Journal of Planar Chromatography – Modern TLC, vol. 33, no. 3, pp. 313-319.
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Sharma, A, Sethi, G, Tambuwala, MM, Aljabali, AAA, Chellappan, DK, Dua, K & Goyal, R 2020, 'Circadian Rhythm Disruption and Alzheimer’s Disease: The Dynamics of a Vicious Cycle', Current Neuropharmacology, vol. 19, no. 2, pp. 248-264.
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:All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
Sharma, AK, Prasher, P, Aljabali, AA, Mishra, V, Gandhi, H, Kumar, S, Mutalik, S, Chellappan, DK, Tambuwala, MM, Dua, K & Kapoor, DN 2020, 'Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy', Drug Delivery and Translational Research, vol. 10, no. 5, pp. 1171-1190.
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Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis. Graphical abstract.
Sharma, M, Prasher, P, Mehta, M, Zacconi, FC, Singh, Y, Kapoor, DN, Dureja, H, Pardhi, DM, Tambuwala, MM, Gupta, G, Chellappan, DK, Dua, K & Satija, S 2020, 'Probing 3CL protease: Rationally designed chemical moieties for COVID‐19', Drug Development Research, vol. 81, no. 8, pp. 911-918.
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Shrivastava, G, Bakshi, HA, Aljabali, AA, Mishra, V, Hakkim, FL, Charbe, NB, Kesharwani, P, Chellappan, DK, Dua, K & Tambuwala, MM 2020, 'Nucleic Acid Aptamers as a Potential Nucleus Targeted Drug Delivery System', Current Drug Delivery, vol. 17, no. 2, pp. 101-111.
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Background:Nucleus targeted drug delivery provides several opportunities for the treatmentof fatal diseases such as cancer. However, the complex nucleocytoplasmic barriers pose significantchallenges for delivering a drug directly and efficiently into the nucleus. Aptamers representing singlestrandedDNA and RNA qualify as next-generation highly advanced and personalized medicinal agentsthat successfully inhibit the expression of certain proteins; possess extraordinary gene-expression formanoeuvring the diseased cell's fate with negligible toxicity. In addition, the precisely directed aptamersto the site of action present a tremendous potential to reach the nucleus by escaping the ensuingbarriers to exhibit a better drug activity and gene expression.Objective:This review epigrammatically highlights the significance of targeted drug delivery and presentsa comprehensive description of the principal barriers faced by the nucleus targeted drug deliveryparadigm and ensuing complexities thereof. Eventually, the progress of nucleus targeting with nucleicacid aptamers and success achieved so far have also been reviewed.Method: Systematic literature search was conducted of research published to date in the field of nucleicacid aptamers.Conclusion: The review specifically points out the contribution of individual aptamers as the nucleustargetingagent rather than aptamers in conjugated form.
Singh, Y, Gupta, G, Kazmi, I, Al‐Abbasi, FA, Negi, P, Chellappan, DK & Dua, K 2020, 'SARS CoV‐2 aggravates cellular metabolism mediated complications inCOVID‐19 infection', Dermatologic Therapy, vol. 33, no. 6.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.
Singh, Y, Gupta, G, Mishra, A, Chellappan, DK & Dua, K 2020, 'Gender and Age Differences Reveal Risk Patterns in COVID-19 Outbreak.', Altern Ther Health Med, vol. 26, no. S2, pp. 54-55.
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By April 28th 2020, the global number of people that were viciously infected with the newfound novel corona virus (COVID-19) stood at a staggering 3 077 133 cases, as per the confirmed data released by the WHO. It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases. Thus, there might be severe myocarditis, that may result in acute heart failure and cardiac complexities in the elderly subjects.
Singh, Y, Gupta, G, Satija, S, Pabreja, K, Chellappan, DK & Dua, K 2020, 'COVID‐19 transmission through host cell directed network of GPCR', Drug Development Research, vol. 81, no. 6, pp. 647-649.
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Solanki, N, Mehta, M, Chellappan, DK, Gupta, G, Hansbro, NG, Tambuwala, MM, AA Aljabali, A, Paudel, KR, Liu, G, Satija, S, Hansbro, PM, Dua, K & Dureja, H 2020, 'Antiproliferative Effects of Boswellic acid-loaded Chitosan Nanoparticles on Human Lung Cancer Cell Line A549', Future Medicinal Chemistry, vol. 12, no. 22, pp. 2019-2034.
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Aim: In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. Methodology & results: The designed nanoparticles were observed spherical in shape with an average size of 67.5–187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC50value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG0phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
Soon, L, Ng, PQ, Chellian, J, Madheswaran, T, Panneerselvam, J, Hsu, A, Hansbro, PM, Dua, K, Collet, T & Chellappan, DK 2020, 'Green synthesis and antibacterial potential of artemisia vulgaris extract in silver nanoparticles against wound bacteria', Jurnal Ilmiah Farmasi, vol. 16, no. 1, pp. 9-18.
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Tan, YY, Yap, PK, Xin Lim, GL, Mehta, M, Chan, Y, Ng, SW, Kapoor, DN, Negi, P, Anand, K, Singh, SK, Jha, NK, Lim, LC, Madheswaran, T, Satija, S, Gupta, G, Dua, K & Chellappan, DK 2020, 'Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics', Chemico-Biological Interactions, vol. 329, pp. 109221-109221.
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Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics propert...
Tew, XN, Xin Lau, NJ, Chellappan, DK, Madheswaran, T, Zeeshan, F, Tambuwala, MM, Aljabali, AAA, Balusamy, SR, Perumalsamy, H, Gupta, G, Oliver, BG, Hsu, A, Wark, P, Reddy, K, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases', Chemico-Biological Interactions, vol. 317, pp. 108947-108947.
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© 2020 Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
Thakur, AK, Chellappan, DK, Dua, K, Mehta, M, Satija, S & Singh, I 2020, 'Patented therapeutic drug delivery strategies for targeting pulmonary diseases', Expert Opinion on Therapeutic Patents, vol. 30, no. 5, pp. 375-387.
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Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.
Thangavelu, L, Balusamy, SR, Shanmugam, R, Sivanesan, S, Devaraj, E, Rajagopalan, V, Veeraiyan, DN, Chellappan, DK, Dua, K, Kim, Y-J & Perumalsamy, H 2020, 'Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model', Regulatory Toxicology and Pharmacology, vol. 113, pp. 104640-104640.
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Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.
Waghule, T, Sankar, S, Rapalli, VK, Gorantla, S, Dubey, SK, Chellappan, DK, Dua, K & Singhvi, G 2020, 'Emerging role of nanocarriers based topical delivery of anti‐fungal agents in combating growing fungal infections', Dermatologic Therapy, vol. 33, no. 6.
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The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
Werth, BL, Fisher, MJ, Williams, KA & Pont, LG 2020, 'Chronic Constipation in the Community', Journal of Wound, Ostomy & Continence Nursing, vol. 47, no. 3, pp. 259-264.
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PURPOSE:The aim of this study was to determine the prevalence of chronic constipation and identify factors associated with chronic constipation in community-dwelling adults.DESIGN:Cross-sectional study.METHODS:The target population was community-dwelling Australian adults; 1978 participants completed an online questionnaire exploring symptoms, management, and factors potentially associated with constipation. Chronic constipation was identified using Rome III criteria. Multivariate logistic regression model was used to identify factors associated with chronic constipation.RESULTS:The prevalence of chronic constipation was 23.9%. Factors significantly associated with chronic constipation in the multivariate model were female gender (odds ratio [OR] = 1.42, 95% confidence interval [CI], 1.12-1.81), current employment (OR = 1.45, 95% CI, 1.11-1.88), regular smoking (OR = 1.60, 95% CI, 1.19-2.14), poor self-rated health (OR = 2.57, 95% CI, 1.28-5.19), thyroid disease (OR = 1.77, 95% CI, 1.21-2.79), depression (OR = 1.49, 95% CI, 1.08-2.06), hemorrhoids (OR = 2.98, 95% CI, 1.84-4.83), irritable bowel syndrome (OR = 2.45, 95% CI, 1.73-3.46), and use of anti-inflammatory/antirheumatic medications (OR = 2.06, 95% CI, 1.15-3.68). In contrast to these factors, use of medications acting on the renin-angiotensin system was associated with a reduced likelihood of chronic constipation (OR = 0.47, 95% CI, 0.24-0.91).CONCLUSIONS:Chronic constipation is prevalent among community-dwelling adults. Various factors associated with chronic constipation have been identified, and knowledge of these factors may help health care professionals recognize individuals who are at high risk of ch...
Werth, BL, Williams, KA, Fisher, MJ & Pont, LG 2020, 'Use of over-the-counter laxatives by community-dwelling adults to treat and prevent constipation: a national cross-sectional study', European Journal of Clinical Pharmacology, vol. 76, no. 7, pp. 1003-1010.
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© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Constipation is commonly self-managed with over-the-counter laxatives. The study aim was to explore laxative choice, healthcare professional recommendations in laxative selection, and laxative effectiveness when laxatives are used for treatment and for prevention of constipation by community-dwelling adults. Methods: A nationally representative sample of community-dwelling adults in Australia was surveyed. Participants completed an online questionnaire. Z tests for differences in proportions were used to compare the proportion of laxatives by class when used either for treatment or for prevention of constipation by choice of laxative, healthcare professional recommendation, and perceived effectiveness. Results: The questionnaire was completed by 2024 participants. Laxatives were used by 37% (n = 747) of participants with 31.3% using laxatives for treatment, 19.3% for prevention, and 49.7% using laxatives for both purposes. The most common laxatives used for treatment and prevention were contact laxatives (39.8% and 31.1% respectively) and bulk-forming laxatives (34.3% and 44.6% respectively). Of all laxatives used, 56.4% of laxatives were chosen with healthcare professional recommendation, and 53.5% of laxatives were found effective. Conclusion: Laxatives were used both for treatment and for prevention of constipation. However, laxatives are often perceived to be ineffective and healthcare professionals are not always involved in laxative choice. Modified guidelines which address the use of laxatives for both treatment and prevention, and increased healthcare professional involvement in appropriate choice and use of laxatives, may be required to improve constipation management in the community.
Wiecek, E, Torres-Robles, A, Cutler, RL, Benrimoj, SI & Garcia-Cardenas, V 2020, 'Impact of a Multicomponent Digital Therapeutic Mobile App on Medication Adherence in Patients with Chronic Conditions: Retrospective Analysis', Journal of Medical Internet Research, vol. 22, no. 8, pp. e17834-e17834.
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Background Strategies to improve medication adherence are widespread in the literature; however, their impact is limited in real practice. Few patients persistently engage long-term to improve health outcomes, even when they are aware of the consequences of poor adherence. Despite the potential of mobile phone apps as a tool to manage medication adherence, there is still limited evidence of the impact of these innovative interventions. Real-world evidence can assist in minimizing this evidence gap. Objective The objective of this study was to analyze the impact over time of a previously implemented digital therapeutic mobile app on medication adherence rates in adults with any chronic condition. Methods A retrospective observational study was performed to assess the adherence rates of patients with any chronic condition using Perx Health, a digital therapeutic that uses multiple components within a mobile health app to improve medication adherence. These components include gamification, dosage reminders, incentives, educational components, and social community components. Adherence was measured through mobile direct observation of therapy (MDOT) over 3-month and 6-month time periods. Implementation adherence, defined as the percentage of doses in which the correct dose of a medication was taken, was assessed across the study periods, in addition to timing adherence or percentage of doses taken at the appropriate time (±1 hour). The Friedman test was used to compare differences in adherence rates over time. Results We analyzed 243 and 130 patients who used the app fo...
Wiecek, E, Torres-Robles, A, Cutler, RL, Benrimoj, SI & Garcia-Cardenas, V 2020, 'Impact of a Multicomponent Digital Therapeutic Mobile App on Medication Adherence in Patients with Chronic Conditions: Retrospective Analysis (Preprint)'.
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BACKGROUND Strategies to improve medication adherence are widespread in the literature; however, their impact is limited in real practice. Few patients persistently engage long-term to improve health outcomes, even when they are aware of the consequences of poor adherence. Despite the potential of mobile phone apps as a tool to manage medication adherence, there is still limited evidence of the impact of these innovative interventions. Real-world evidence can assist in minimizing this evidence gap.
OBJECTIVE The objective of this study was to analyze the impact over time of a previously implemented digital therapeutic mobile app on medication adherence rates in adults with any chronic condition.
METHODS A retrospective observational study was performed to assess the adherence rates of patients with any chronic condition using Perx Health, a digital therapeutic that uses multiple components within a mobile health app to improve medication adherence. These components include gamification, dosage reminders, incentives, educational components, and social community components. Adherence was measured through mobile direct observation of therapy (MDOT) over 3-month and 6-month time periods. Implementation adherence, defined as the percentage of doses in which the correct dose of a medication was taken, was assessed across the study periods, in addition to timing adherence or percentage of doses taken at the appropriate time (±1 hour). The Friedman test was used to compare differences in adherence rates over time.
RESULTS <...
Wong, J-Y, Yin Ng, Z, Mehta, M, Shukla, SD, Panneerselvam, J, Madheswaran, T, Gupta, G, Negi, P, Kumar, P, Pillay, V, Hsu, A, Hansbro, NG, Wark, P, Bebawy, M, Hansbro, PM, Dua, K & Chellappan, DK 2020, 'Curcumin-Loaded Niosomes Downregulate mRNA Expression of Pro-Inflammatory Markers Involved in Asthma: An In Vitro Study', Nanomedicine, vol. 15, no. 30, pp. 2955-2970.
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Aim: In this study, curcumin was encapsulated in niosomes (Nio-Curc) to increase its effectiveness for the treatment of asthma. Materials & methods: The formulation underwent various physicochemical characterization experiments, an in vitro release study, molecular simulations and was evaluated for in vitro anti-inflammatory activity. Results: Results showed that Nio-Curc had a mean particle size of 284.93 ± 14.27 nm, zeta potential of -46.93 and encapsulation efficacy of 99.62%, which demonstrates optimized physicochemical characteristics. Curcumin release in vitro could be sustained for up to 24 h. Additionally, Nio-Curc effectively reduced mRNA transcript expression of pro-inflammatory markers; IL-6, IL-8, IL-1β and TNF-α in immortalized human airway basal cell line (BCi-NS1.1). Conclusion: In this study, we have demonstrated that Nio-Curc mitigated the mRNA expression of pro-inflammatory markers in an in vitro study, which could be applied to treatment of asthma with further studies.
Xu, J, Xu, X, Jiang, L, Dua, K, Hansbro, PM & Liu, G 2020, 'SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis', Respiratory Research, vol. 21, no. 1.
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AbstractBackgroundSevere acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPRSS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood.MethodsThe networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients.ResultsWe confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients.ConclusionsTherefore, S...
Yong, DOC, Saker, SR, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Choudhury, H, Pandey, M, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2020, 'Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin', Endocrine, Metabolic & Immune Disorders - Drug Targets, vol. 20, no. 10, pp. 1590-1596.
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The application of medicinal plants has captured the interest of researchers in recent timesdue to their potent therapeutic properties and a better safety profile. The prominent role of herbal productsin treating and preventing multiple diseases dates back to ancient history and most of the moderndrugs today originated from their significant sources owing to their ability to control multiple targetsvia different signalling pathways. Among them, flavonoids consist of a large group of polyphenols,which are well known for their various therapeutic benefits. Rutin is considered one of the attractivephytochemicals and important flavonoids in the pharmaceutical industry due to its diverse pharmacologicalactivities via various underlying molecular mechanisms. It is usually prescribed for variousdisease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, wehave discussed and highlighted the different molecular mechanisms attributed to the various pharmacologicalactivities of rutin, such as antioxidant, anti-inflammatory, anticancer, anti-allergic and antidiabetic.This review will be beneficial to herbal, biological and molecular scientists in understandingthe pharmacological relevance of rutin at the molecular level.
Yong, FR, Garcia-Cardenas, V, Williams, KA & (Charlie) Benrimoj, SI 2020, 'Factors affecting community pharmacist work: A scoping review and thematic synthesis using role theory', Research in Social and Administrative Pharmacy, vol. 16, no. 2, pp. 123-141.
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© 2019 Elsevier Inc. Many community pharmacists ideologically support recent changes to their roles in primary healthcare. However, their antithetical resistance towards practice change could have systemic causes (i.e. role stresses), which may account for increased job dissatisfaction, burnout, and job turnover in the profession. Deeper comprehension was sought using a role theory framework. Objective: To identify factors leading to role stresses and strain responses for community pharmacists, and to create a framework for community pharmacist role management. Method: PubMed, Scopus and Web of Science databases were searched for qualitative studies identifying community pharmacist role stress and strain using scoping review methodology from 1990 to 2019. Content and thematic analysis using the framework method was performed, and themes were reported using thematic synthesis. Results: Screening of 10,880 records resulted in 33 studies identified, with 41 factors categorised into four domains: Interpersonal Interactions, Social Setting, Individual Attributes, and Extra-Role. All role stresses were present. Reported role strains suggest role system imbalance. Conclusion: Community pharmacists are in a multifactorial transitional environment. Reported role stresses may be a function of past pharmacist roles and increased role expectations, amplified by many requisite interactions and individual pharmacist characteristics. Social science theories were found to be applicable to the community pharmacy setting.
