Aldryhim, AY, Alomair, A, Alqhtani, M, Mahmoud, MA, Alshammari, TM, Pont, LG, Kamal, KM, Aljadhey, H, Mekonnen, AB, Alwhaibi, M, Balkhi, B & Alhawassi, TM 2019, 'Factors that facilitate reporting of adverse drug reactions by pharmacists in Saudi Arabia', Expert Opinion on Drug Safety, vol. 18, no. 8, pp. 745-752.
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Objectives: Adverse drug reactions (ADRs) are a pervasive global problem, and its management is integral to patient safety and healthcare quality. Pharmacists play a pivotal role in monitoring and reporting ADRs, which has a direct impact on patient care. The aim of this study was to identify potential factors that facilitate pharmacists in community and hospital settings to report ADRs. Methods: A cross-sectional, online survey using a validated questionnaire was administered to pharmacists working in community and hospital pharmacies in Saudi Arabia. Results: 1,717 community and 153 hospital pharmacists participated in this study. Only 10.2% and 26.8% of community and hospital pharmacists, respectively, admitted ever reporting an ADR. The most reported factors that may facilitate ADRs reporting have included ongoing improvements in therapeutic knowledge about ADRs, attending educational programs with continuous medical education credits, the seriousness of the experienced ADRs and accessibility to patients' medical profile. The impact of peers by seeing colleagues reporting ADRs and ADRs due to herbal or traditional medicine were the least important factors reported by pharmacists. Conclusion: The study identified factors that can effectively address the under-reporting of ADRs by pharmacists. A multi-stakeholder, multi-pronged approach of ADR reporting is needed to develop greater awareness of this issue among pharmacists.
Aly, M, García-Cárdenas, V, Williams, KA & Benrimoj, SI 2019, 'A qualitative study of stakeholder views and experiences of minor ailment services in the United Kingdom', Research in Social and Administrative Pharmacy, vol. 15, no. 5, pp. 496-504.
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© 2018 Elsevier Inc. Background: An international strategy designed to promote access to primary care is the utilisation of community pharmacy to deliver structured minor ailment services (MASs). An understanding of key implementation features of MASs will support effective service delivery and implementation, promote MAS viability, sustainability and overall improvement. Aim: The aim of this study is to explore the views and experiences of a range of stakeholders concerning the implementation of MASs in the United Kingdom. Methods: A qualitative approach was used to obtain data. Participants were recruited using purposeful and snowball sampling. Stakeholders from five different regions were included. Using the digital recordings of the interviews, thematic content analysis was undertaken. Results: Thirty-three participants agreed to be interviewed. Twenty-nine semi-structured interviews were conducted. Thematic content analysis yielded three major themes, including (1)benefits of MASs, (2)structural challenges associated with MAS design and (3)other implementation factors associated with MAS delivery. Stakeholders recognised the positive impact of the service to improve patient access and care, promote efficiencies, and promote the professional role of the pharmacist. Nevertheless barriers do exist to service delivery and implementation. Stakeholders identified the need to potentially increase the population groups served by MASs, increase the conditions treated and widen their formulary lists. Similarly, marketing strategies needed to be improved to enhance consumer awareness. Stakeholders presented mixed views about whether pharmacists needed to complete clinical training and the need to increase pharmacist's remuneration. In addition the level of healthcare collaboration needed to improve. Conclusion: Several concepts emerged from the investigation to facilitate service delivery. Barriers to service implementation had a variable impact on implementa...
Amador-Fernández, N, Benrimoj, SI, Baixauli Fernández, VJ, Climent Catalá, MT, Colomer Molina, V, Esteban Jiménez, Ó, Fernández San José, B, García Agudo, Ó, García Cárdenas, V, García García, JI, Gastelurrutia, MÁ, Gómez Martínez, JC, Valls Roca, F & Martínez Martínez, F 2019, 'Colaboración farmacéutico-médico en la elaboración de protocolos consensuados para el tratamiento de síntomas menores: programa ‘INDICA+PRO’', Farmacéuticos Comunitarios, vol. 11, no. 4, pp. 21-31.
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Baixauli Fernandez, VJ, Abellan-Garcia Sanchez, F, Molinero Crespo, A, Prats Mas, R, Plaza Zamora, J, Gaztelurrutia Lavesa, L, Bellver Beltran, S, Arranz Esteban, MDM, Garcia-Espona Pancorbo, JL, Cremades Alcaraz, J & Amador Fernandez, N 2019, 'Information to patients on professional pharmaceutical care services of Community Pharmacy', FARMACEUTICOS COMUNITARIOS, vol. 11, no. 3, pp. 22-41.
Bakshi, HA, Mishra, V, Satija, S, Mehta, M, Hakkim, FL, Kesharwani, P, Dua, K, Chellappan, DK, Charbe, NB, Shrivastava, G, Rajeshkumar, S, Aljabali, AA, Al-Trad, B, Pabreja, K & Tambuwala, MM 2019, 'Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis', Inflammation, vol. 42, no. 6, pp. 2032-2036.
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Benson, H, Lucas, C, Benrimoj, SI & Williams, KA 2019, 'The development of a role description and competency map for pharmacists in an interprofessional care setting', International Journal of Clinical Pharmacy, vol. 41, no. 2, pp. 391-407.
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Background Pharmacists are increasingly being included as members of general practice primary care teams. To date, there have been few published studies describing the competencies of general practice (GP) pharmacists and establishing their subsequent educational needs. Aim of the review The aim of this literature review is to establish the activities of pharmacists in general practice to inform the development of a comprehensive role description and competency map. Method A systematic literature search of EMBASE, MEDLINE, international pharmaceutical abstracts and the Cochrane database of systematic reviews was conducted from the start of the databases to August 2018. The search focused on studies investigating the roles performed by GP pharmacists. Full text peer-reviewed English language articles were included. A qualitative content analysis of included studies was performed. Two researchers reviewed studies to identify pharmacist roles. Subcategories of roles were then agreed by the research team and used to present the data. GP pharmacist's activities were mapped by two researchers to associated competencies. Any discrepancies between role descriptions and competency maps were resolved in consultation with a third member of the research team. Results The search conducted resulted in 5370 potential articles. Two hundred and twenty-seven full text articles were selected for review resulting in 34 articles that were included for analysis. Seven GP pharmacist role sub-categories and 48 GP pharmacist individual roles were identified. The seven GP pharmacist role sub-categories included medication management, patient examination and screening, chronic disease management, drug information and education, collaboration and liaison, audit and quality assurance and research. All FIP competency domains were included in the GP pharmacist competency map. Competencies related to compounding, dispensing and packaging of medications were not found relevant to the GP Pharmaci...
Bugno, A, Almodovar, AAB, Saes, DPS, Awasthi, R, Ghisleni, DDM, de Souza Braga, M, de Oliveira, WA, Dua, K & de Jesus Andreoli Pinto, T 2019, 'Evaluation of an Amplified ATP Bioluminescence Method for Rapid Sterility Testing of Large Volume Parenteral', Journal of Pharmaceutical Innovation, vol. 14, no. 2, pp. 152-158.
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The sterility test described in pharmacopeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the Celsis AKuScreen™ Advance™ system, is particularly interesting because it allows a reduced incubation period and higher efficiency. The present study was aimed to evaluate and compare the performance of Celsis AKuScreen™ Advance™ system with the pharmacopeial sterility test. There was no significant difference between the ability of detection of microbial contamination observed within pharmacopeial method and test method. The Celsis AKuScreen™ Advance™ system allowed a faster detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.
Chellappan, DK, Sze Ning, QL, Su Min, SK, Bin, SY, Chern, PJ, Shi, TP, Ee Mei, SW, Yee, TH, Qi, OJ, Thangavelu, L, Rajeshkumar, S, Negi, P, Chellian, J, Wadhwa, R, Gupta, G, Collet, T, Hansbro, PM & Dua, K 2019, 'Interactions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases', Chemico-Biological Interactions, vol. 310, pp. 108732-108732.
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© 2019 Elsevier B.V. Background: The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases. Methods: Relevant published studies, literature and reports were searched from accessible electronic databases and related institutional databases. We used keywords, viz; microbiome, microbiota, microbiome drug delivery and respiratory disease. Selected articles were carefully read through, clustered, segregated into subtopics and reviewed. Findings: The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage,...
Chellappan, DK, Yee, NJ, Kaur Ambar Jeet Singh, BJ, Panneerselvam, J, Madheswaran, T, Chellian, J, Satija, S, Mehta, M, Gulati, M, Gupta, G & Dua, K 2019, 'Formulation and Characterization of Glibenclamide and quercetin-loaded Chitosan Nanogels Targeting Skin Permeation', Therapeutic Delivery, vol. 10, no. 5, pp. 281-293.
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Aim: Our aim was to develop and characterize a nanogel formulation containing both glibenclamide and quercetin and to explore the permeation profile of this combination. Methods: Drug-loaded nanogel was prepared by ionic gelation. In addition, optimum encapsulation efficiencies of glibenclamide and quercetin were also obtained. The average nanoparticle size at optimum conditions was determined by Zetasizer. Results: The particle size of the nanogel was found to be 370.4 ± 4.78 nm with a polydispersity index of 0.528 ± 0.04, while the λ potential was positive in a range of 17.6 to 24.8 mV. The percentage cumulative drug release also showed favorable findings. Conclusion: The chitosan nanogel could be a potential alternative for delivering glibenclamide and quercetin through skin.
Cherk Yong, DO, Saker, SR, Wadhwa, R, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Tambuwala, MM, Bakshi, HA, Kumar, P, Pillay, V, Gupta, G, Oliver, BG, Wark, P, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2019, 'Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma', Journal of Drug Delivery Science and Technology, vol. 54, pp. 101297-101297.
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© 2019 Elsevier B.V. The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma.
Cutler, RL, der Linden, NV, (Charlie) Benrimoj, SI, Fernandez-Llimos, F & Garcia-Cardenas, V 2019, 'An evidence-based model to consolidate medication adherence cost estimation: the medication adherence cost estimation framework', Journal of Comparative Effectiveness Research, vol. 8, no. 8, pp. 555-567.
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Aim:To develop a standardized framework determining the economic impact of medication nonadherence.Materials & methods:Secondary analysis of existing literature reported cost data, aggregating cost outcome indicators. Weighted-average cost analysis performed, determining the proportional contribution to total cost.Results:Direct costs were reported in 92% of studies and indirect costs in 4% of studies. Three most utilized cost categories were hospital (68%), primary care (18%) and pharmacy costs (72%). Average unadjusted direct costs ranged from $625 to $154,203 contributing to 88% of the total cost; adjusted medical costs ranged from $565 to $56,313 representing 96% of the total cost.Conclusion:The medication adherence cost estimation framework enables the comparison of costing studies, facilitating informed health policy decision-making based on consistent evidence and terminology.
Cutler, RL, Torres-Robles, A, Wiecek, E, Drake, B, Van der Linden, N, Benrimoj, SIC & Garcia-Cardenas, V 2019, '<p>Pharmacist-led medication non-adherence intervention: reducing the economic burden placed on the Australian health care system</p>', Patient Preference and Adherence, vol. Volume 13, pp. 853-862.
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© 2019 Cutler et al. Background: Scarcity of prospective medication non-adherence cost measurements for the Australian population with no directly measured estimates makes determining the burden medication non-adherence places on the Australian health care system difficult. This study aims to indirectly estimate the national cost of medication non-adherence in Australia comparing the cost prior to and following a community pharmacy-led intervention. Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n=11,257 on rosuvastatin, n=6,797 on irbesartan and n=2,281 on desvenlafaxine) was analyzed and average adherence rate determined through calculation of PDC. Included patients received a pharmacist-led medication adherence intervention and had twelve months dispensing records; six months before and six months after the intervention. The national cost estimate of medication non-adherence in hypertension, dyslipidemia and depression pre-and post-intervention was determined through utilization of disease prevalence and comorbidity, non-adherence rates and per patient disease-specific adherence-related costs. Results: The total national cost of medication non-adherence across three prevalent conditions, hypertension, dyslipidemia and depression was $10.4 billion equating to $517 per adult. Following enrollment in the pharmacist-led intervention medication non-adherence costs per adult decreased $95 saving the Australian health care system and patients $1.9 billion annually. Conclusion: In the absence of a directly measured national cost of medication non-adherence, this estimate demonstrates that pharmacists are ideally placed to improve patient adherence and reduce financial burden placed on the health care system due to non-adherence. Funding of medication adherence programs should be considered by policy and decision makers to ease the current burden and improve patient health outcomes moving forward.
Das, P, Kumar, K, Nambiraj, A, Awasthi, R, Dua, K & Malipeddi, H 2019, 'Antibacterial and In Vitro Growth Inhibition Study of Struvite Urinary Stones Using Oxalis corniculata Linn. Leaf Extract and its Biofabricated Silver Nanoparticles', Recent Patents on Drug Delivery & Formulation, vol. 12, no. 3, pp. 170-178.
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Herbal drugs are gaining exponential scientific recognition due to their distinct advantages. In the last 2-3 decades, a gradual increase in worldwide patents on herbal nano-formulations has been noted to address the solubility and bioavailability issues of phytoceuticals. Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO4.6H2O) is among the important urinary infection stones causing painful urological ailment. These smaller stones may bind together to form a bigger staghorn calculi. Urinary tract infections caused by some gram positive and gram negative bacteria further enhances the chance of formation of such stones. Oxalis corniculata Linn. is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones. However, there is no scientific evidence to relate the use of O. corniculata against struvite kidney stones. Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn. leaves and its biofabricated silver nanoparticles (AgNPs) was studied.The aqueous extract of O. corniculata was prepared by Soxhlet extraction. AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies. Antibacterial activity of the aqueous extract and the silver nanoparticles were tested against E. coli (gram negative) and S. aureus (gram positive) species. Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles..The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria. The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs.The present work confirms the inhib...
De Rubis, G, Rajeev Krishnan, S & Bebawy, M 2019, 'Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis', Trends in Pharmacological Sciences, vol. 40, no. 3, pp. 172-186.
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© 2019 Elsevier Ltd Liquid biopsies, comprising the noninvasive analysis of circulating tumor-derived material (the ‘tumor circulome’), represent an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies. Within the tumor circulome, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are the only components the clinical application of which is approved by the US Food and Drug Administration (FDA). Extracellular vesicles (EVs), circulating tumor RNA (ctRNA), and tumor-educated platelets (TEPs) are relatively new tumor circulome constituents with promising potential at each stage of cancer management. Here, we discuss the clinical applications of each element of the tumor circulome and the prevailing factors that currently limit their implementation in clinical practice. We also detail the most recent technological developments in the field, which demonstrate potential in improving the clinical value of liquid biopsies.
Dighe, SN, Ekwudu, O, Dua, K, Chellappan, DK, Katavic, PL & Collet, TA 2019, 'Recent update on anti-dengue drug discovery', European Journal of Medicinal Chemistry, vol. 176, pp. 431-455.
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© 2019 Elsevier Masson SAS Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014–2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
Dineen-Griffin, S, Garcia-Cardenas, V, Rogers, K, Williams, K & Benrimoj, SI 2019, 'Evaluation of a Collaborative Protocolized Approach by Community Pharmacists and General Medical Practitioners for an Australian Minor Ailments Scheme: Protocol for a Cluster Randomized Controlled Trial', JMIR Research Protocols, vol. 8, no. 8, pp. e13973-e13973.
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Background Internationally, governments have been investing in supporting pharmacists to take on an expanded role to support self-care for health system efficiency. There is consistent evidence that minor ailment schemes (MASs) promote efficiencies within the health care system. The cost savings and health outcomes demonstrated in the United Kingdom and Canada open up new opportunities for pharmacists to effect sustainable changes through MAS delivery in Australia. Objective This trial aims to evaluate the clinical, economic, and humanistic impact of an Australian Minor Ailments Service (AMAS) compared with usual pharmacy care in a cluster randomized controlled trial (cRCT) in Western Sydney, Australia. Methods The cRCT design has an intervention group and a control group, comparing individuals receiving a structured intervention (AMAS) with those receiving usual care for specific health ailments. Participants will be community pharmacies, general practices, and patients located in Western Sydney Primary Health Network (WSPHN) region. A total of 30 community pharmacies will be randomly assigned to either intervention or control group. Each will recruit 24 patients, aged 18 years or older, presenting to the pharmacy in person with a symptom-based or product-based request for one of the following ailments: reflux, cough, common cold, headache (tension or migraine), primary dysmenorrhea, or low back pain. Intervention pharmacists will deliver protocolized care to patients using clinical treatment pathways with agreed referral points and collaborative systems boosting clinician-pharmacist communication. Patients recruited in control pharmacies will receive usual care. The copr...
Dineen-Griffin, S, Garcia-Cardenas, V, Williams, K & Benrimoj, SI 2019, 'Helping patients help themselves: A systematic review of self-management support strategies in primary health care practice', PLOS ONE, vol. 14, no. 8, pp. e0220116-e0220116.
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© 2019 Dineen-Griffin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Primary health professionals are well positioned to support the delivery of patient self-management in an evidence-based, structured capacity. A need exists to better understand the active components required for effective self-management support, how these might be delivered within primary care, and the training and system changes that would subsequently be needed. Objectives (1) To examine self-management support interventions in primary care on health outcomes for a wide range of diseases compared to usual standard of care; and (2) To identify the effective strategies that facilitate positive clinical and humanistic outcomes in this setting. Method A systematic review of randomized controlled trials evaluating self-management support interventions was conducted following the Cochrane handbook & PRISMA guidelines. Published literature was systematically searched from inception to June 2019 in PubMed, Scopus and Web of Science. Eligible studies assessed the effectiveness of individualized interventions with follow-up, delivered face-to-face to adult patients with any condition in primary care, compared with usual standard of care. Matrices were developed that mapped the evidence and components for each intervention. The methodological quality of included studies were appraised. Results 6,510 records were retrieved. 58 studies were included in the final qualitative synthesis. Findings reveal a structured patient-provider exchange is required in primary care (including a one-on-one patient-provider consultation, ongoing follow up and provision of self-help materials). Interventions should be tailored to patient needs and may include combinations of strategies to improve a patient’s d...
Dua, K, Malyla, V, Singhvi, G, Wadhwa, R, Krishna, RV, Shukla, SD, Shastri, MD, Chellappan, DK, Maurya, PK, Satija, S, Mehta, M, Gulati, M, Hansbro, N, Collet, T, Awasthi, R, Gupta, G, Hsu, A & Hansbro, PM 2019, 'Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems', Chemico-Biological Interactions, vol. 299, pp. 168-178.
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© 2018 Elsevier B.V. Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
Dua, K, Wadhwa, R, Singhvi, G, Rapalli, V, Shukla, SD, Shastri, MD, Gupta, G, Satija, S, Mehta, M, Khurana, N, Awasthi, R, Maurya, PK, Thangavelu, L, S, R, Tambuwala, MM, Collet, T, Hansbro, PM & Chellappan, DK 2019, 'The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress', Drug Development Research, vol. 80, no. 6, pp. 714-730.
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AbstractLung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti‐inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post‐transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro‐inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
Gautam, RK, Gupta, G, Sharma, S, Hatware, K, Patil, K, Sharma, K, Goyal, S, Chellappan, DK & Dua, K 2019, 'Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats, using Freund’s complete adjuvant', International Journal of Rheumatic Diseases, vol. 22, no. 7, pp. 1247-1254.
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AbstractAimThe purpose of our investigation is to evaluate the anti‐arthritic potential of isolated rosmarinic acid from the rind of Punica granatum.MethodRosmarinic acid was isolated by bioactivity‐guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)‐induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor‐α (TNF‐α) were also estimated.ResultsRosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF‐α were observed in treated groups as compared to arthritic control rats (P < 0.001). At the same time antioxidant parameters (like GSH and SOD) were increased significantly while levels of MDA were significantly decreased (P < 0.001).ConclusionThe outcome of the present research concludes that rosmarinic acid showed significant anti‐arthritic potential in FCA‐induced arthritis in Wistar rats. This study represented the therapeutic role of rosmarinic acid from Punica granatum for the management of arthritis/rheumatoid arthritis/osteoarthritis and related inflammatory complications with negligible side effects which ...
Gupta, G, Pathak, S, Dahiya, R, Awasthi, R, Mishra, A, Sharma, RK, Agrawal, M & Dua, K 2019, 'Aqueous Extract of Wood Ear Mushroom, Auricularia polytricha (Agaricomycetes), Demonstrated Antiepileptic Activity against Seizure Induced by Maximal Electroshock and Isoniazid in Experimental Animals', International Journal of Medicinal Mushrooms, vol. 21, no. 1, pp. 29-35.
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Auricularia polytricha is a popular mushroom found all over the world. This article describes a study of the antiepileptic effect of A. polytricha, a mushroom that is used traditionally for treating asthma, rheumatism, tumors, cough, fever, and epilepsy, and for its antimicrobial effect. We carried out toxicity studies to identify a standard dose of A. polytricha aqueous extract; maximal electroshock (MES)- and isoniazid (INH)-induced seizures in albino mice were used to screen for the extract's antiepileptic activity. Per Organisation for Economic Co-operation and Development Guideline 423, up to 2000 mg/kg body weight of extract was toxic. Animals were treated with aqueous extract at doses of 200, 400, and 600 mg/kg body weight. Phenytoin was used as the reference anticonvulsant drug for comparison. The investigation found a significant interruption in INH-induced clonic seizure. During MES, we found a reduction in the period of hind leg extensor phase; mice exhibited a significant decrease in the duration of hind limb extension after being treated with 400 and 600 mg/kg doses of A. polytricha. Comparable results were obtained in the INH group, as the extract seemed to delay the onset of a clonic seizure. The aqueous extract of A. polytricha showed antiepileptic action against MES- and INH-induced epilepsy in the mice. This extract, however, requires additional study in order to completely explain its active ingredients and their mechanisms of action.
Heer, S, Jindal, S, Mishra, G, Madan, JR, Gupta, G, AWASTHI, DR, Pinto, TDJA, Dua, K & Kulkarni, GT 2019, 'Formulation and characterization of oral rapid disintegrating tabletsof levocetirizine', Polymers in Medicine, vol. 48, no. 1, pp. 31-40.
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Background
Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure.
Objectives
The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with β-cyclodextrin (β-CD).
Material and methods
Levocetirizine-β-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution.
Results
A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia.
Conclusions
Complexation of levocetirizine with β-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.
Khursheed, R, Singh, SK, Wadhwa, S, Kapoor, B, Gulati, M, Kumar, R, Ramanunny, AK, Awasthi, A & Dua, K 2019, 'Treatment strategies against diabetes: Success so far and challenges ahead', European Journal of Pharmacology, vol. 862, pp. 172625-172625.
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© 2019 Elsevier B.V. The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail.
Kumari, Y, Kaur, G, Kumar, R, Singh, SK, Gulati, M, Khursheed, R, Clarisse, A, Gowthamarajan, K, Karri, VVSNR, Mahalingam, R, Ghosh, D, Awasthi, A, Kumar, R, Yadav, AK, Kapoor, B, Singh, PK, Dua, K & Porwal, O 2019, 'Gold nanoparticles: New routes across old boundaries', Advances in Colloid and Interface Science, vol. 274, pp. 102037-102037.
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In recent years, gold nanoparticles have emerged as unique non-invasive drug carriers for targeting drugs to their site of action. Their site specificity has helped in increasing drugs' efficacy at lower dose as well as reduction in their side effects. Moreover, their excellent optical properties and small size offer their utilization as diagnostic tools to diagnose tumors as well as other diseases. This review focuses on various approaches that have been used in last several years for preparation of gold nanoparticles, their characterization techniques and theranostic applications. Their toxicity related aspects are also highlighted. Gold nanoparticles are useful as theranostic agents, owing to their small size, biocompatible nature, size dependent physical, chemical and optical properties etc. However, the challenges associated with these nanoparticles such as scale up, cost, low drug payload, toxicity and stability have been the major impediments in their commercialization. The review looks into all these critical issues and identifies the possibilities to overcome these challenges for successful positioning of metallic nanoparticles in market.
Lucas, C, Williams, K & Bajorek, B 2019, 'Virtual Pharmacy Programs to Prepare Pharmacy Students for Community and Hospital Placements', American Journal of Pharmaceutical Education, vol. 83, no. 10, pp. 7011-7011.
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Objective. To explore and evaluate pharmacy students' perceptions of the value and relevance of virtual community and virtual hospital on-campus placement programs. Methods. Students enrolled in a Master of Pharmacy program completed the required Virtual Community Placement (VCP) program and/or the Virtual Hospital Placement (VHP) program. A six-item questionnaire was administered to students after completion of each of the virtual programs to elicit students' perceptions of the value and relevance of the virtual programs. Additional data related to the relevance of specific workshops were collected, including students' self-reported confidence levels to undertake placement in a real-world setting following completion of the virtual programs. Results. Surveys were completed by 61 students in the VCP program and 50 students in the VHP program. Students perceived the virtual programs to be beneficial, with the majority (84% of the VCP students and 98% of the VHP students) reporting that the programs should be an essential component of any pharmacy degree. The majority of students (72%) self-reported an increase in their confidence levels in undertaking a real-world experiential placement after they completed their virtual hospital placement. Conclusion. Completing virtual placement programs prior to pharmacy students beginning their first "real world" pharmacy placements had a positive effect on student learning and confidence levels. Pharmacy students' feedback from this study regarding the relevance of specific learning modules and laboratory sessions will inform future curriculum development of the virtual placement programs.
Lucas, C, Woulfe, J, Lonie, JM, Williams, KA & Smith, L 2019, 'Pharmacy students’ perceptions of ePortfolios in pharmacy education', Pharmacy Education, vol. 19, no. 1, pp. 162-170.
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Aims: To investigate perceptions of an ePortfolio structure, its utility to support pharmacy student learning, development of reflective capacity, and attainment of professional competencies. Methods: Mixed-methods two-phase study: Phase 1 (Quantitative): pre- and post-use, 6-item student survey; Phase 2 (Qualitative): 45-minute student focus group. Survey (n=49, RR 82%) and focus group respondents (n=12) provided their perceptions of ePortfolios. Statistically significant findings between Week 1 and Week 14 indicated that in addition to a time consuming exercise, students perceived that the current structure of the ePortfolio did not fully support their learning; development of their reflective capacity; self-directed learning skills; and professional practice. Conclusions: Pharmacy students perceived the ePortfolio needed improvements to reach its full potential. Students indicated that maintaining an ePortfolio is a useful tool to track professional competencies, linking digital evidence and reflections. Proposed suggestions were identified for improvement that would enable them to meet curricular competencies.
Madan, JR, Dagade, RH, Awasthi, R & Dua, K 2019, 'Formulation and solid state characterization of carboxylic acid-based co-crystals of tinidazole: An approach to enhance solubility', Polymers in Medicine, vol. 48, no. 2, pp. 99-104.
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BACKGROUND:Tinidazole (TNZ) is an anti-parasite drug used in the treatment of a variety of amebic and parasitic infections. It has low solubility in aqueous media and is categorized under Class II of the Biopharmaceutical Classification System. OBJECTIVES:The aim of this research was to study the potential for enhancing the solubility of TNZ using carboxylic acid co-crystals. MATERIAL AND METHODS:The solubility of TNZ was determined individually using 6 carboxylic acids for forming co-crystals at a 1:1 stoichiometric ratio. Three carboxylic acids - namely tartaric acid (TA), oxalic acid (OA) and glutaric acid (GA) - resulted in the formation of co-crystals with enhanced solubility. An equilibrium solubility study of TNZ co-crystals at 1:1.5 and 1:2 stoichiometric ratios was also carried out. The co-crystals which developed were evaluated using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) to study the drug-co-crystal former interactions. RESULTS:The solubility of TNZ in distilled water was found to be 0.014 mg/mL. The highest enhancement ratio was obtained with TNZ and TA at a ratio of 1:1. Differential scanning calorimetry thermograms suggested that the drug and carboxylic acids had undergone interactions such as hydrogen bonding. The XRD and DSC results confirmed the formation of co-crystals. CONCLUSIONS:It was concluded that the results of enhanced solubility of TNZ using co-crystals is a clear indication of the potential for co-crystals to be used in the future for other poorly water-soluble drugs, considering that co-crystals are a safe and cost-effective approach.
Madan, JR, Pawar, AR, Patil, RB, Awasthi, R & Dua, K 2019, 'Preparation, characterization and in vitro evaluationof tablets containing microwave-assisted solid dispersions of apremilast', Polymers in Medicine, vol. 48, no. 1, pp. 17-24.
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BACKGROUND:Solid dispersions are among the techniques successfully employed to enhance the dissolution of poorly water-soluble drugs. Microwave (MW)-assisted evaporative crystallization has been used to prepare solid dispersions of drugs and polymers. OBJECTIVES:The aim of the study was to investigate the solubility of apremilast (APM) in water by exploring the effect of MW-assisted solid dispersion technology. MATERIAL AND METHODS:In the present study, solid dispersions of APM, a poorly water-soluble drug, were prepared. The solid dispersions were prepared using the conventional method (CM) and the MW-based solvent evaporation technique. Microwave energy was used to enhance the solubility and dissolution rate of APM. The physical mixture and solid dispersions were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Apremilast tablets containing MW-assisted solid dispersions were prepared by the direct compression technique and compared with the marketed formulation (Aprezo tablets). RESULTS:The results obtained confirmed the conversion of crystalline APM to an amorphous form. The XRPD pattern of the MW-assisted formulation at a 2:1 ratio suggests the amorphous structure of APM within the formulation. Based on solubility studies results, Syloid® 244FP was selected as the best carrier. The dissolution study results suggested that the APM tablet prepared using MW-assisted solid dispersions at a 2:1 carrier/drug ratio improved the APM dissolution rate compared to the marketed formulation. CONCLUSIONS:Based on the results, it can be concluded that the MW-assisted solid dispersion technique may be an effective approach to enhancing the dissolution profile of other poorly water-soluble drugs.
Martínez‐Mardones, F, Fernandez‐Llimos, F, Benrimoj, SI, Ahumada‐Canale, A, Plaza‐Plaza, JC, S. Tonin, F & Garcia‐Cardenas, V 2019, 'Systematic Review and Meta‐Analysis of Medication Reviews Conducted by Pharmacists on Cardiovascular Diseases Risk Factors in Ambulatory Care', Journal of the American Heart Association, vol. 8, no. 22.
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Background Pharmacists‐led medication reviews ( MRs ) are claimed to be effective for the control of cardiovascular diseases; however, the evidence in the literature is conflicting. The main objective of this meta‐analysis was to analyze the impact of pharmacist‐led MRs on cardiovascular disease risk factors overall and in different ambulatory settings while exploring the effects of different components of MRs . Methods and Results Searches were conducted in PubMed, Web of Science, Embase, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library Central Register of Controlled Trials database. Randomized and cluster randomized controlled trials of pharmacist‐led MRs compared with usual care were included. Settings were community pharmacies and ambulatory clinics. The classification used for MRs was the Pharmaceutical Care Network Europe as basic (type 1), intermediate (type 2), and advanced (type 3). Meta‐analyses in therapeutic goals used odds ratios to standardize the effect of each study, and for continuous data (eg, systolic blood pressure) raw differences were calculated using baseline and final values, with 95% CI s. P...
Mehta, DK, Taya, P, Das, R & Dua, K 2019, 'Design, Synthesis and Molecular Docking Studies of Novel Thiadiazole Analogues with Potential Antimicrobial and Antiinflammatory Activities', Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, vol. 18, no. 2, pp. 91-109.
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Background:Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities.Methods:A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy.Results:Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac.Conclusion:The experimental results were further supported by molecular docking analysis describing the better interaction patterns.
Mehta, M, Deeksha, Sharma, N, Vyas, M, Khurana, N, Maurya, PK, Singh, H, Andreoli de Jesus, TP, Dureja, H, Chellappan, DK, Gupta, G, Wadhwa, R, Collet, T, Hansbro, PM, Dua, K & Satija, S 2019, 'Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases', Chemico-Biological Interactions, vol. 304, pp. 10-19.
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© 2019 Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
Mehta, M, Deeksha, Tewari, D, Gupta, G, Awasthi, R, Singh, H, Pandey, P, Chellappan, DK, Wadhwa, R, Collet, T, Hansbro, PM, Kumar, SR, Thangavelu, L, Negi, P, Dua, K & Satija, S 2019, 'Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases', Chemico-Biological Interactions, vol. 308, pp. 206-215.
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© 2019 Elsevier B.V. Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
Mohanta, S, Singh, SK, Kumar, B, Gulati, M, Kumar, R, Yadav, AK, Wadhwa, S, Jyoti, J, Som, S, Dua, K & Pandey, NK 2019, 'Efficacy of co-administration of modified apple polysaccharide and probiotics in guar gum-Eudragit S100 based mesalamine mini tablets: A novel approach in treating ulcerative colitis', International Journal of Biological Macromolecules, vol. 126, pp. 427-435.
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© 2018 Elsevier B.V. Modified Apple Polysaccharide (MAP) has been reported to cure colorectal diseases by up-regulating apoptosis and down regulating metastasis. In the present study, mesalamine (MES) and MAP mini tablets have been prepared and co-administered with probiotics to provide site specific release of drug. Probiotics along with MAP, which acts as a prebiotic would replenish the colonic microflora that have been compromised due to colorectal pathology. MES mini tablets were prepared keeping guar gum in the core and coating them with Eudragit S100 and guar gum. The optimized batch was explored for its curative potential on acetic acid induced ulcerative colitis (UC) in rat model with and without administration of probiotic and MAP. The results revealed that the rats treated with the combination of MAP and MES mini tablets along with probiotics show maximum curative potential. It was also observed that MAP mini tablets show better curative potential as compared to probiotics. The results of disease activity index, macroscopic scoring, antioxidant studies, tumour alpha and histopathological examination suggested that the rats treated with combination of MES-MAP mini tablets and probiotics have maximum therapeutic effect followed by MES mini tablets alone, MAP mini tablets alone and probiotics.
Ng, SW, Chan, Y, Chellappan, DK, Madheswaran, T, Zeeshan, F, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Panneerselvam, J 2019, 'Molecular modulators of celastrol as the keystones for its diverse pharmacological activities', Biomedicine & Pharmacotherapy, vol. 109, pp. 1785-1792.
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© 2018 The Authors In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
Pandey, P, Chellappan, DK, Tambuwala, MM, Bakshi, HA, Dua, K & Dureja, H 2019, 'Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system', International Journal of Biological Macromolecules, vol. 141, pp. 596-610.
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The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer.
Pandey, P, Dua, K & Dureja, H 2019, 'Erlotinib loaded chitosan nanoparticles: Formulation, physicochemical characterization and cytotoxic potential', International Journal of Biological Macromolecules, vol. 139, pp. 1304-1316.
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© 2019 Elsevier B.V. Cancer is the major cause of mortality and morbidity throughout the world where >10 million patients with new cases diagnosed every year. The objective of this study was to prepare and evaluate erlotinib loaded chitosan nanoparticles for their anticancer potential. Also, to study the effect of various formulation variables on prepared nanoparticles using box-behnken design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using the spray drying technique. It was found that batch SNP-9 has a maximum loading capacity (74.45 ± 0.34%) and entrapment efficiency (43 ± 0.57%) with a particle size 170.2 nm. Analysis of variance (ANOVA) was applied on the particle size, entrapment efficiency and % cumulative drug release to study the fitting and the significance of the model. The batch SNP-9 showed 89.46% and 40.12% drug release after 24 h in 0.1 N HCl and Phosphate Buffer (pH 6.8), respectively. The IC50 value of SNP-9 evaluated on A549 Lung cancer cells was found to be 4.41 μM. The optimized formulation was found stable after the six-month study as no considerable transformation was detected. The optimized formulation released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using spray drying technique with suitable particle size, entrapment efficiency, drug release. The synthesized and optimized nanoparticles were found to possess activity against cancer cells when evaluated in-vitro.
Pont, LG, Fisher, M & Williams, K 2019, 'Appropriate Use of Laxatives in the Older Person', Drugs & Aging, vol. 36, no. 11, pp. 999-1005.
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Constipation is a common condition, affecting up to half of all older adults during their lifetime. Untreated constipation has significant impacts, decreasing quality of life and potentially leading to urinary and/or faecal incontinence, faecal impaction and, in severe cases, hospitalisation. The increased constipation prevalence among older populations is multifactorial, with a number of age-related factors contributing to the rise in prevalence with aging. Laxatives are the mainstay of constipation management and are commonly used among older populations for both treatment and prevention of constipation. A range of laxative types including bulk forming agents, softeners and emollients, osmotic agents, stimulants, and the newer prokinetic and secretory agents are available. Despite laxatives being freely available without prescription in many countries and commonly used by older individuals, evidence regarding the effectiveness or safety of most laxatives in older populations is lacking. Additionally, age-related changes increase the risk of adverse effects associated with laxatives, such as electrolyte disturbances, among older persons. Caution must be taken when extrapolating recommendations for general adult populations to older populations. Laxative choice for older individuals should be tailored after careful assessment and consideration of comorbid conditions, concomitant medications and the potential for adverse effects.
Pottegård, A, Klungel, O, Winterstein, A, Huybrechts, K, Hallas, J, Schneeweiss, S, Evans, S, Bate, A, Pont, L, Trifirò, G, Smith, M & Bourke, A 2019, 'The International Society for Pharmacoepidemiology's Comments on the Core Recommendations in the Summary of the Heads of Medicines Agencies (HMA) ‐ EMA Joint Big Data Task Force', Pharmacoepidemiology and Drug Safety, vol. 28, no. 12, pp. 1640-1641.
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Pradhan, R, Singhvi, G, Dubey, SK, Gupta, G & Dua, K 2019, 'MAPK Pathway: a Potential Target for the Treatment of Non-small-cell Lung Carcinoma', Future Medicinal Chemistry, vol. 11, no. 8, pp. 793-795.
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Raban, MZ, Walter, SR, Pont, LG, Cheung, L, Strumpman, D & Westbrook, JI 2019, 'The potential impact of an electronic medication management system on safety‐critical prescribing errors in an emergency department', Journal of Pharmacy Practice and Research, vol. 49, no. 2, pp. 108-115.
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AbstractBackgroundMedication errors in hospitals are common. Although electronic medication management systems (eMMS) have the potential to reduce errors during inpatient care, little is known about their effect in emergency departments (ED).AimThe aims of this study were to report on the types of prescribing errors in an ED prior to implementation of an eMMS, to assess the risk the errors pose to patient safety and to evaluate whether safety‐critical errors were potentially preventable with a newly implemented eMMS.MethodsMedication orders on paper charts were assessed for prescribing errors by a clinical hospital pharmacist. Error severity was rated using a five‐point scale. Errors of moderate or higher severity, and all errors involving defined high‐risk medicines were considered safety‐critical errors. The potential for safety‐critical errors to be prevented by the eMMS was rated (likely, possibly or unlikely).ResultsAcross 239 medication orders, 208 errors (27 clinical, 181 legal or procedural) were identified. The overall prescribing error rate was 0.87 errors/order. There were 67 safety‐critical errors (53 legal or procedural, 14 clinical). Overall, 82.1% of errors were likely preventable by eMMS. However, of the clinical safety‐critical errors, only 2 (14.3%) were con...
Rajeshkumar, S, Menon, S, Venkat Kumar, S, Tambuwala, MM, Bakshi, HA, Mehta, M, Satija, S, Gupta, G, Chellappan, DK, Thangavelu, L & Dua, K 2019, 'Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract', Journal of Photochemistry and Photobiology B: Biology, vol. 197, pp. 111531-111531.
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© 2019 Elsevier B.V. Environment friendly methods for the synthesis of copper nanoparticles have become a valuable trend in the current scenario. The utilization of phytochemicals from plant extracts has become a unique technology for the synthesis of nanoparticles, as they possess dual nature of reducing and capping agents to the nanoparticles. In the present investigation we have synthesized copper nanoparticles (CuNPs) using a rare medicinal plant Cissus arnotiana and evaluated their antibacterial activity against gram negative and gram positive bacteria. The morphology and characterization of the synthesized CuNPs were studied and done using UV-Visible spectroscopy at a wavelength range of 350–380 nm. XRD studies were performed for analyzing the crystalline nature; SEM and TEM for evaluating the spherical shape within the size range of 60–90 nm and AFM was performed to check the surface roughness. The biosynthesized CuNPs showed better antibacterial activity against the gram-negative bacteria, E. coli with an inhibition zone of 22.20 ± 0.16 mm at 75 μg/ml. The antioxidant property observed was comparatively equal with the standard antioxidant agent ascorbic acid at a maximum concentration of 40 μg/ ml. This is the first study reported on C. arnotiana mediated biosynthesis of copper nanoparticles, where we believe that the findings can pave way for a new direction in the field of nanotechnology and nanomedicine where there is a significant potential for antibacterial and antioxidant activities. We predict that, these could lead to an exponential increase in the field of biomedical applications, with the utilization of green synthesized CuNPs, due to its remarkable properties. The highest antibacterial property was observed with gram-negative strains mainly, E. coli, due to its thin peptidoglycan layer and electrostatic interactions between the bacterial cell wall and CuNPs surfaces. Hence, CuNPs can be potent therapeutic agents in several biomedical ...
Sah, SK, Samuel, VP, Dahiya, S, Singh, Y, Gilhotra, RM, Gupta, G, Mishra, A, Sharma, RK, Kumar, GS, SreeHarsha, N, Chellappan, DK & Dua, K 2019, 'A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia', Chemico-Biological Interactions, vol. 306, pp. 117-122.
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Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.
Salehi, B, Staniak, M, Czopek, K, Stępień, A, Dua, K, Wadhwa, R, Kumar Chellappan, D, Sytar, O, Brestic, M, Ganesh Bhat, N, Venkatesh Anil Kumar, N, del Mar Contreras, M, Sharopov, F, C. Cho, W & Sharifi-Rad, J 2019, 'The Therapeutic Potential of the Labdane Diterpenoid Forskolin', Applied Sciences, vol. 9, no. 19, pp. 4089-4089.
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Forskolin is mainly found in the root of a plant called Coleus forskohlii (Willd.) Briq., which has been used in the traditional medicine of Indian Ayurvedic and Southeast Asia since ancient times. Forskolin is responsible for the pharmacological activity of this species. Forskolin is a labdane diterpenoid with a wide biological effect. Several studies suggested a positive role of forskolin on heart complications, respiratory disorders, high blood pressure, obesity, and asthma. There are numerous clinical and pre-clinical studies representing the effect of forskolin on the above-mentioned disorders but more clinical studies need to be performed to support its efficacy.
Samuel, VP, Dahiya, R, Singh, Y, Gupta, G, Sah, SK, Gubbiyappa, SK, Chellappan, DK & Dua, K 2019, 'Metformin: A Salutary Candidate for Colorectal Cancer Treatment in Patients with Diabetes', Journal of Environmental Pathology, Toxicology and Oncology, vol. 38, no. 2, pp. 133-141.
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Samuel, VP, Gupta, G, Dahiya, R, Jain, DA, Mishra, A & Dua, K 2019, 'Current Update on Preclinical and Clinical Studies of Resveratrol, a Naturally Occurring Phenolic Compound', Critical Reviews in Eukaryotic Gene Expression, vol. 29, no. 6, pp. 529-537.
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Resveratrol has several therapeutic effects and is a nutraceutical. It was shown to imitate caloric restriction effects, exert anti-inflammatory and antioxidative effects, and affect the development and progression of many diseases through several mechanisms. While there is a wealth of evidence in vitro and in vivo that resveratrol could be a promising therapeutic agent, its potential must be confirmed by preclinical studies and clinical trials. We analyzed the current available preclinical and clinical data on resveratrol's pharmacological action. The bulk of resveratrol's preclinical studies and clinical trials focused on cancer, neurological disorders, cardiovascular diseases, diabetes, nonalcoholic fatty liver disease (NAFLD), and obesity. The latest preclinical studies and clinical trials reported that resveratrol was well tolerated and beneficially influenced biomarkers of disease for neurological disorders, cardiovascular diseases, and diabetes. Nevertheless, in certain types of cancers and in NAFLD, resveratrol had unclear and sometimes even detrimental effects. The major obstacle posed in most preclinical studies and clinical trials was the low bioavailability of resveratrol. This work thus provides useful guidelines for future preclinical and clinical resveratrol study planning and design.
Sharma, P, Mehta, M, Dhanjal, DS, Kaur, S, Gupta, G, Singh, H, Thangavelu, L, Rajeshkumar, S, Tambuwala, M, Bakshi, HA, Chellappan, DK, Dua, K & Satija, S 2019, 'Emerging trends in the novel drug delivery approaches for the treatment of lung cancer', Chemico-Biological Interactions, vol. 309, pp. 108720-108720.
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© 2019 Elsevier B.V. Cancer is one of the major diseases that cause a high number of deaths globally. Of the major types of cancers, lung cancer is known to be the most chronic form of cancer in the world. The conventional management of lung cancer includes different medical interventions like chemotherapy, surgical removal, and radiation therapy. However, this type of approach lacks specificity and also harms the adjacent normal cells. Lately, nanotechnology has emerged as a promising intervention in the management and treatment of lung cancers. Nanotechnology has revolutionized the existing modalities and focuses primarily on reducing toxicity and improving the bioavailability of anticancer drugs to the target tumor cells. Nanocarrier systems are being currently used extensively to exploit and to overcome the obstructions induced by cancers in the lungs. The nano-carrier-loaded therapeutic drug delivery methods have shown promising potential in treating lung cancer as its target is to control the growth of tumor cells. In this review, various modes of nano drug delivery options like liposomes, dendrimers, quantum dots, carbon nanotubes and metallic nanoparticles have been discussed. Nano-carrier drug delivery systems emerge as a promising approach and thus is expected to provide newer and advanced avenues in cancer therapeutics.
Sheshala, R, Ming, NJ, Kok, YY, Raj Singh, TR & Dua, K 2019, 'Formulation and Characterization of pH Induced in situ Gels Containing Sulfacetamide Sodium for Ocular Drug Delivery: A Combination of Carbopol®/ HPMC Polymer', Indian Journal of Pharmaceutical Education and Research, vol. 53, no. 4, pp. 654-662.
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Shukla, SD, Shastri, MD, Chong, WC, Dua, K, Budden, KF, Mahmood, MQ, Hansbro, NG, Keely, S, Eri, R, Patel, RP, Peterson, GM & Hansbro, PM 2019, 'Microbiome-focused asthma management strategies', Current Opinion in Pharmacology, vol. 46, pp. 143-149.
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© 2019 Elsevier Ltd Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times. Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal, although its’ roles are poorly understood when assessing the asthma progression or heterogeneity (i.e. phenotypes/endotypes) across different geographical locations. Moreover, modulating microbiomes could be preventive and/or therapeutic in patients with asthma warrants urgent attention. Here, we review recent advances in assessing the role of microbiomes in asthma and present the challenges associated with the potential therapeutic utility of modifying microbiomes in management.
Singh, Y, Samuel, VP, Dahiya, S, Gupta, G, Gillhotra, R, Mishra, A, Singh, M, SreeHarsha, N, Gubbiyappa, SK, Tambuwala, MM, Chellappan, DK & Dua, K 2019, 'Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia‐associated hypertension', Biotechnology and Applied Biochemistry, vol. 66, no. 5, pp. 715-719.
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AbstractHomocysteine [HSCH2CH2CH(NH2)COOH] (Hcy) is a sulfur‐containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta‐analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin‐converting enzyme inhibitors angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia‐associated hypertension.
Soon, L, Ng, PQ, Chellian, J, Madheswaran, T, Panneerselvam, J, Gupta, G, Nammi, S, Hansbro, NG, Hsu, A, Dureja, H, Mehta, M, Satija, S, Hansbro, PM, Dua, K, Collet, T & Chellappan, DK 2019, 'Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms', Journal of Environmental Pathology, Toxicology and Oncology, vol. 38, no. 3, pp. 205-216.
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© 2019 by Begell House, Inc. Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.
Tan, WT, Kopecky, C, Manandhar, B, Rye, KA & Cochran, B 2019, 'Skeletal Muscle Specific Deletion Of Abca1 And Abcg1 Impacts Body Composition And Metabolism And Is Age Dependent', Atherosclerosis, vol. 287, pp. e43-e43.
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Torres-Robles, A, Wiecek, E, Cutler, R, Drake, B, Benrimoj, SI, Fernandez-Llimos, F & Garcia-Cardenas, V 2019, 'Using Dispensing Data to Evaluate Adherence Implementation Rates in Community Pharmacy', Frontiers in Pharmacology, vol. 10, no. FEB, p. 130.
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Copyright © 2019 Torres-Robles, Wiecek, Cutler, Drake, Benrimoj, Fernandez-Llimos and Garcia-Cardenas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Background: Medication non-adherence remains a significant problem for the health care system with clinical, humanistic and economic impact. Dispensing data is a valuable and commonly utilized measure due accessibility in electronic health data. The purpose of this study was to analyze the changes on adherence implementation rates before and after a community pharmacist intervention integrated in usual real life practice, incorporating big data analysis techniques to evaluate Proportion of Days Covered (PDC) from pharmacy dispensing data. Methods: Retrospective observational study. A de-identified database of dispensing data from 20,335 patients (n = 11,257 on rosuvastatin, n = 6,797 on irbesartan, and n = 2,281 on desvenlafaxine) was analyzed. Included patients received a pharmacist-led medication adherence intervention and had dispensing records before and after the intervention. As a measure of adherence implementation, PDC was utilized. Analysis of the database was performed using SQL and Python. Results: Three months after the pharmacist intervention there was an increase on average PDC from 50.2% (SD: 30.1) to 66.9% (SD: 29.9) for rosuvastatin, from 50.8% (SD: 30.3) to 68% (SD: 29.3) for irbesartan and from 47.3% (SD: 28.4) to 66.3% (SD: 27.3) for desvenlafaxine. These rates declined over 12 months to 62.1% (SD: 32.0) for rosuvastatin, to 62.4% (SD: 32.5) for irbesartan and to 58.1% (SD: 31.1) for desvenla...
Usman, B, Sharma, N, Satija, S, Mehta, M, Vyas, M, Khatik, GL, Khurana, N, Hansbro, PM, Williams, K & Dua, K 2019, 'Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update', Current Pharmaceutical Design, vol. 25, no. 23, pp. 2510-2525.
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The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.
van der Meer, HG, Taxis, K, Teichert, M, Griens, F, Pont, LG & Wouters, H 2019, 'Anticholinergic and sedative medication use in older community‐dwelling people: A national population study in the Netherlands', Pharmacoepidemiology and Drug Safety, vol. 28, no. 3, pp. 315-321.
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AbstractPurposeTo identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)‐active medication used.MethodsA cross‐sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS‐active medications used were identified with latent class analysis.ResultsOverall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS‐active medications used: “combined psycholeptic/psychoanaleptic medication” (class 1, 57.9%), “analgesics” (class 2, 17.9%), “antiepileptic medication” (class 3, 17.8%), and “anti‐Parkinson medication” (class 4, 6.3%).ConclusionsA large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS‐active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.
van der Meer, HG, Wouters, H, Teichert, M, Griens, F, Pavlovic, J, Pont, LG & Taxis, K 2019, 'Feasibility, acceptability and potential effectiveness of an information technology-based, pharmacist-led intervention to prevent an increase in anticholinergic and sedative load among older community-dwelling individuals', Therapeutic Advances in Drug Safety, vol. 10, pp. 204209861880588-204209861880588.
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Background: Anticholinergic/sedative medications are frequently used by older people, despite their negative impacts on cognitive and physical function. We explore the feasibility, acceptability and potential effectiveness of an innovative information technology (IT)-based intervention to prevent an increase in anticholinergic/sedative load in older people. Methods: This was a prospective study in 51 Dutch community pharmacies. Pharmacists used an IT-based tool to identify patients aged ⩾65 years, with existing high anticholinergic/sedative loads (drug burden index ⩾2) and a newly initiated anticholinergic/sedative medication. We determined the following. Feasibility: number of eligible patients identified. Acceptability: pharmacists’ satisfaction with the intervention, pharmacists’ time investment and patients’ willingness to reduce medication use. Potential effectiveness: number of recommendations, rate of agreement of general practitioners (GPs) with proposed recommendations and factors associated with agreement. To evaluate the latter, pharmacists conducted medication reviews and proposed recommendations to GPs for 5–10 patients selected by the IT-based tool. Results: We included 305 patients from 47 pharmacies. Feasibility: a mean of 17.0 (standard deviation, 8.8) patients were identified per pharmacy. Acceptability: 43 pharmacists (91.5%) were satisfied with the intervention. The median time investment per patient was 33 min (range 6.5–210). Of 35 patients, 30 (85.7%) were willing to reduce medication use. Potential effectiveness: pharmacists proposed 351 recommendations for 212 patients (69.5%). GPs agreed with recommendations for 108 patients (35.4%). Agreement to stop a medication was reached in 19.8% of recommendations for newly initiated medications (37 of 187) and for 15.2% o...
Wadhwa, R, Aggarwal, T, Malyla, V, Kumar, N, Gupta, G, Chellappan, DK, Dureja, H, Mehta, M, Satija, S, Gulati, M, Maurya, PK, Collet, T, Hansbro, PM & Dua, K 2019, 'Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease', Journal of Cellular Physiology, vol. 234, no. 10, pp. 16703-16723.
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AbstractChronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome‐wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator‐like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9).
Wadhwa, R, Dua, K, Adcock, IM, Horvat, JC, Kim, RY & Hansbro, PM 2019, '“Cellular mechanisms underlying steroid-resistant asthma.” Ridhima Wadhwa, Kamal Dua, Ian M. Adcock, Jay C. Horvat, Richard Y. Kim and Philip M. Hansbro.Eur Respir Rev2019; 28: 190021.', European Respiratory Review, vol. 28, no. 154, pp. 195096-195096.
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Wadhwa, R, Dua, K, Adcock, IM, Horvat, JC, Kim, RY & Hansbro, PM 2019, 'Cellular mechanisms underlying steroid-resistant asthma', European Respiratory Review, vol. 28, no. 153, pp. 190096-190096.
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Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.
Wadhwa, R, Pandey, P, Gupta, G, Aggarwal, T, Kumar, N, Mehta, M, Satija, S, Gulati, M, Madan, JR, Dureja, H, Balusamy, SR, Perumalsamy, H, Maurya, PK, Collet, T, Tambuwala, MM, Hansbro, PM, Chellappan, DK & Dua, K 2019, 'Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species', Current Topics in Medicinal Chemistry, vol. 19, no. 28, pp. 2593-2609.
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Background:Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections.Methods:The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.Results:This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.).Conclusion:It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.
Waghule, T, Singhvi, G, Dubey, SK, Pandey, MM, Gupta, G, Singh, M & Dua, K 2019, 'Microneedles: A smart approach and increasing potential for transdermal drug delivery system', Biomedicine & Pharmacotherapy, vol. 109, pp. 1249-1258.
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© 2018 Elsevier Masson SAS The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.
Werth, BL, Williams, KA, Fisher, MJ & Pont, LG 2019, 'Defining constipation to estimate its prevalence in the community: results from a national survey', BMC Gastroenterology, vol. 19, no. 1.
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BACKGROUND:Different definitions of constipation have been used to estimate its prevalence in the community but this creates difficulties when comparing results from various studies. This study explores the impact of different definitions on prevalence estimates in the same population and compares the performance of simple definitions with the Rome III criteria. METHODS:The prevalence of constipation in a large nationally representative sample of community-dwelling adults was estimated using five simple definitions of constipation and compared with definitions based on the Rome III criteria. The sensitivity, specificity, and positive and negative predictive values, were calculated for each definition using the Rome III criteria as the gold standards for chronic and sub-chronic constipation. RESULTS:Prevalence estimates for the five simple definitions ranged from 9.4 to 58.9%, while the prevalence estimates using the Rome III criteria were 24.0% (95%CI: 22.1, 25.9) for chronic constipation and 39.6% (95%CI: 37.5, 41.7) for sub-chronic constipation. None of the simple definitions were adequate compared to the Rome III criteria. Self-reported constipation over the past 12 months had the highest sensitivity (91.1%, 95%CI: 88.8, 93.4) and negative predictive value (94.5%, 95%CI: 93.1, 96.1) compared to the Rome III criteria for chronic constipation but an unacceptably low specificity (51.3%, 95%CI: 48.8, 53.8) and positive predictive value (37.1%, 95%CI: 34.4, 39.9). CONCLUSIONS:The definition used to identify constipation within a population has a considerable impact on the prevalence estimate obtained. Simple definitions, commonly used in research, performed poorly compared with the Rome III criteria. Studies estimating population prevalence of constipation should use definitions based on the Rome criteria where possible.
Xin, GLL, Khee, YP, Ying, TY, Chellian, J, Gupta, G, Kunnath, AP, Nammi, S, Collet, T, Hansbro, PM, Dua, K & Chellappan, DK 2019, 'Current Status on Immunological Therapies for Type 1 Diabetes Mellitus', Current Diabetes Reports, vol. 19, no. 5, p. 22.
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Type 1 diabetes (T1D) occurs when there is destruction of beta cells within the islets of Langerhans in the pancreas due to autoimmunity. It is considered a complex disease, and different complications can surface and worsen the condition if T1D is not managed well. Since it is an incurable disease, numerous treatments and therapies have been postulated in order to control T1D by balancing hyperglycemia control while minimizing hypoglycemic episodes. The purpose of this review is to primarily look into the current state of the available immunological therapies and their advantages for the treatment of T1D. Recent Findings: Over the years, immunological therapy has become the center of attraction to treat T1D. Immunomodulatory approaches on non-antigens involving agents such as cyclosporine A, mycophenolate mofetil, anti-CD20, cytotoxic T cells, anti-TNF, anti-CD3, and anti-thymocyte globulin as well as immunomodulative approaches on antigens such as insulin, glutamic acid decarboxylase, and heat shock protein 60 have been studied. Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D. Many of these agents have successfully suppressed T1D in non-obese diabetic (NOD) mice and in human trials. However, some have shown negative results. Summary: To date, the insights into the management of the immune system have been increasing rapidly to search for potential therapies and treatments for T1D. Nevertheless, some of the challenges are still inevitable. A lot of work and effort need to be put into the investigation on T1D through immunological therapy, particularly to reduce complications to improve and enhance clinical outcomes.
Yap, PK, Loo Xin, GL, Tan, YY, Chellian, J, Gupta, G, Liew, YK, Collet, T, Dua, K & Chellappan, DK 2019, 'Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention', Journal of Pharmacy and Pharmacology, vol. 71, no. 9, pp. 1339-1352.
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Abstract Objectives Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. Key findings Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. Summary Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also...
Yeung, S, Traini, D, Tweedie, A, Lewis, D, Church, T & Young, PM 2019, 'Assessing Aerosol Performance of a Dry Powder Carrier Formulation with Increasing Doses Using a Novel Inhaler', AAPS PharmSciTech, vol. 20, no. 3.
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Yeung, S, Traini, D, Tweedie, A, Lewis, D, Church, T & Young, PM 2019, 'Effect of Dosing Cup Size on the Aerosol Performance of High-Dose Carrier-Based Formulations in a Novel Dry Powder Inhaler', Journal of Pharmaceutical Sciences, vol. 108, no. 2, pp. 949-959.
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