Alhawassi, TM, Krass, I & Pont, LG 2018, 'Antihypertensive-related adverse drug reactions among older hospitalized adults', International Journal of Clinical Pharmacy, vol. 40, no. 2, pp. 428-435.
View/Download from: Publisher's site
View description>>
© 2018, Springer International Publishing AG, part of Springer Nature. Background Antihypertensive medications are commonly used for a wide range of indications, yet it is unknown to what extent older adults are at risk of adverse drug reactions (ADRs) associated with their antihypertensive medication use. Objective The aim of this study was to determine the prevalence and characteristics of antihypertensive-related ADRs on hospital admission. Setting Metropolitan teaching hospital in Sydney, Australia. Method A retrospective cross-sectional audit of 503 older patients (≥ 65 years) admitted to hospital was conducted. Potential ADRS were identified from the medical record. Two independent clinical pharmacists reviewed each potential ADR using validated tools for causality, severity, preventability and contribution to hospitalization. Characteristics associated with an increased ADR risk among antihypertensive users were identified via logistic regression. Main outcome measure Antihypertensive related ADRs. Results Antihypertensives were used on admission by 68% of the cohort and the prevalence of ‘definite/probable’ antihypertensive-related ADRs among antihypertensive users was 16.4%. Antihypertensive medications were associated with a threefold ADR risk (OR = 3.09, 95% CI 1.85–5.16). Angiotensin II Receptor Blockers (ARB), impaired renal function, recent medication changes and previous history of allergy or ADR were all associated with an increased risk of experiencing an ADR. Conclusions ADRS associated with antihypertensive medicines were relatively common among older adults admitted to hospital. Increased awareness of those older persons who are most at risk of experiencing an antihypertensive-related ADR in the clinical setting may lead to early detection and minimization of ADR associated harms.
Aly, M, García-Cárdenas, V, Williams, K & Benrimoj, SI 2018, 'A review of international pharmacy-based minor ailment services and proposed service design model', Research in Social and Administrative Pharmacy, vol. 14, no. 11, pp. 989-998.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Inc. Background: The need to consider sustainable healthcare solutions is essential. An innovative strategy used to promote minor ailment care is the utilisation of community pharmacists to deliver minor ailment services (MASs). Promoting higher levels of self-care can potentially reduce the strain on existing resources. Aim: To explore the features of international MASs, including their similarities and differences, and consider the essential elements to design a MAS model. Methods: A grey literature search strategy was completed in June 2017 to comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard. This included (1) Google/Yahoo! search engines, (2) targeted websites, and (3) contact with commissioning organisations. Executive summaries, table of contents and title pages of documents were reviewed. Key characteristics of MASs were extracted and a MAS model was developed. Results: A total of 147 publications were included in the review. Key service elements identified included eligibility, accessibility, staff involvement, reimbursement systems. Several factors need to be considered when designing a MAS model; including contextualisation of MAS to the market. Stakeholder engagement, service planning, governance, implementation and review have emerged as key aspects involved with a design model. Conclusion: MASs differ in their structural parameters. Consideration of these parameters is necessary when devising MAS aims and assessing outcomes to promote sustainability and success of the service.
Andrade, LDO, Awasthi, R, Dua, K & de Jesus Andreoli Pinto, T 2018, 'Matrix-assisted laser desorption ionization–time of flight mass spectrometry for identification of bacteria isolated from pharmaceutical clean rooms', Interventional Medicine and Applied Science, vol. 10, no. 1, pp. 45-53.
View/Download from: Publisher's site
View description>>
Introduction During the manufacturing of sterile drugs, it is of the utmost importance to meet the minimum requirements for asepsis recommended by the legislations on good manufacturing practices-based efficient environmental monitoring. Aims and methods The availability of relatively simple to use matrix-assisted laser desorption ionization–time of flight mass spectromtomy (MALDI-TOF MS) devices in the last years has changed the laboratory workflows for the microbial identification, mainly in the clinical area. Thus, the objective of this work was to evaluate the suitability of the MALDI-TOF MS technique for the identification of bacteria isolated from the environment of clean rooms used in some stages of the production of a viral vaccine. Eighteen known bacterial species commonly isolated from clean rooms studied were identified by MALDI-TOF technique and by a biochemical technique (BBL Crystal® System). Results Performance of MALDI-TOF MS was better than biochemical technique for correct species identifications (88.89% and 38.89%, respectively) and produced less unreliable identification (5.55% and 22.22%). Conclusion MALDI-TOF MS can be implemented for routine identification of bacteria in a pharmaceutical quality control laboratory, but as a database-dependent system, maybe some isolated not identified by this technique must be additionally studied and, if appropriate, added to an in-house database.
Awasthi, R, Rathbone, MJ, Hansbro, PM, Bebawy, M & Dua, K 2018, 'Therapeutic prospects of microRNAs in cancer treatment through nanotechnology', Drug Delivery and Translational Research, vol. 8, no. 1, pp. 97-110.
View/Download from: Publisher's site
View description>>
© 2017, Controlled Release Society. MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due to extensive advancements in knowledge since their discovery and, more recently, their translational application as therapeutic moieties and targets in the management of disease. miRNAs used in the treatment of cancer would position them as a new class of emerging therapeutic agents. Indeed, numerous candidate miRNAs have been identified as having therapeutic application in the treatment of cancer, but there is still much to learn about how to transform these into effective, patient-compliant, and targeted drug delivery systems. In this mini review, we discuss the utility and potential of nanotechnology in miRNA formulation and delivery with particular emphasis on cancer, including their role in conferring multidrug resistance and metastatic capacity. This review benefits both the formulation and biological scientists in understanding and exploring the new vistas of miRNA delivery using nanotechnology in the cancer clinically.
Awasthi, R, Roseblade, A, Hansbro, PM, Rathbone, MJ, Dua, K & Bebawy, M 2018, 'Nanoparticles in Cancer Treatment: Opportunities and Obstacles', Current Drug Targets, vol. 19, no. 14, pp. 1696-1709.
View/Download from: Publisher's site
View description>>
In the United States, the estimated number of new cancer cases in 2018 will be approx. 1.7 million. Historically, combination chemotherapy has been the primary choice of treatment. However, chemotherapeutics have pharmaceutical limitations, among which include problems with stability and aqueous solubility. Likewise, dose limiting toxicity is significant with nonspecific toxicity to healthy cells, hair loss, loss of appetite, peripheral neuropathy and diarrhea being typical side effects. The emergence of Multidrug resistance (MDR) also presents s a significant challenge for the successful treatment of cancer whereby cancer cells become cross resistant to many of the chemotherapeutic agents used. Nanotechnology presents a new frontier for cancer treatment. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. They also provide an alternative strategy to circumvent multidrug resistance as they have a capacity to by-pass the drug efflux mechanism associated with this phenotype. Aside from the advantages they offer in treatment, nanoparticles are also emerging to be valuable diagnostic entities. This article highlights the various ways nanotechnology is being used to improve the treatment and management of cancer. We also discuss the opportunities and obstacles in this area and provide an up to date review of progress in the treatment of cancer.
Balkhi, B, Aljadhey, H, Mahmoud, MA, Alrasheed, M, Pont, LG, Mekonnen, AB & Alhawassi, TM 2018, 'Readiness and willingness to provide immunization services: a survey of community pharmacists in Riyadh, Saudi Arabia', Safety in Health, vol. 4, no. 1.
View/Download from: Publisher's site
Benson, H, Lucas, C, Benrimoj, SI, Kmet, W & Williams, KA 2018, 'Pharmacists in general practice: recommendations resulting from team-based collaborative care', Australian Journal of Primary Health, vol. 24, no. 6, pp. 448-448.
View/Download from: Publisher's site
View description>>
The Western Sydney Primary Health Network (PHN), WentWest, has been working to improve patient and health system outcomes by commissioning projects that enhance patient-focussed, team-based care. One such project is the WentWest General Practice Pharmacist Project, involving the integration of pharmacists within general practice sites. The aim of this study is to describe, classify and analyse recommendations made by pharmacists to GPs, resulting from patient consultations between pharmacists and patients in a general practice setting. This study was a multi-centre prospective observational study (April 2017–September 2017) investigating recommendations made by pharmacists integrated in a general practice setting. Thirteen general practice sites located in Western Sydney, NSW, Australia were involved in the study. The main outcome measures of this study include the classification of pharmacist recommendations and the percentage of those recommendations accepted by GPs. The pharmacists recorded the results from 618 patient consultations. These consultations resulted in 1601 recommendations of which 1404 (88%) were recorded as accepted. This study demonstrated that the recommendations made by pharmacists in general practice are well accepted by GPs and may lead to improvements in medication management and patient care.
Benson, H, Lucas, C, Kmet, W, Benrimoj, SI & Williams, K 2018, 'Pharmacists in general practice: a focus on drug-related problems', International Journal of Clinical Pharmacy, vol. 40, no. 3, pp. 566-572.
View/Download from: Publisher's site
View description>>
Background Team based care has been used internationally to improve the delivery of best practice primary health care. The WentWest General Practice Pharmacist Project, involving the integration of pharmacists within general practice teams, was commissioned to improve medication management of general practice patients. A particular focus of the project was the performance of medication review to allow the detection and resolution of drug related problems (DRPs). Objective The objectives of this 6-month study (October 2016-March 2017) were to: (1) identify and classify the DRPs detected as a result of pharmacist activities within a general practice primary care setting. (2) compare the number of pharmacist recommendations and GP acceptance rates as a result of pharmacist patient consultations across multiple general practice sites. Setting 15 general practice primary care sites in Western Sydney NSW Australia. A multi-centre prospective observational study conducted over a 6-month period from October 2016 to March 2017. Main outcome measure Drug-related problems (DRPs). Results Six pharmacists recorded the results from 493 patient consultations. The pharmacists identified 1124 DRPs and made 984 recommendations, of which 685 (70%) were recorded as accepted by the GP. Conclusion Pharmacists have a valuable role to play in the detection and resolution of DRP as part of the general practice team.
Benson, H, Sabater-Hernández, D, Benrimoj, SI & Williams, KA 2018, 'Piloting the Integration of Non-Dispensing Pharmacists in the Australian General Practice Setting: A Process Evaluation', International Journal of Integrated Care, vol. 18, no. 2, pp. 4-4.
View/Download from: Publisher's site
View description>>
© 2018 The Author(s). Introduction: This process evaluation examined the circumstances affecting implementation, intervention design and situational context of the twelve week pilot phase of a project integrating five pharmacists into twelve general practice sites in Western Sydney. Description of Care Practice: This study used a mixed method study design using qualitative data obtained from semi-structured interviews and quantitative data collected by project pharmacists to analyse the process of the integrating pharmacists is general practice. Framework analysis of the interview transcripts was used to align the results with the key process evaluation themes of implementation, mechanism of impact and context. Preliminary quantitative data was used to provide implementation feedback and to support the qualitative findings. Results: The interventional design included three phases, patient recruitment and selection, the pharmacist consultation and the communication and recording of recommendations. A number of barriers and facilitators affecting implementation were identified. Insight into the situational context of the intervention was gained from examining the differences between individual pharmacists and between practice sites. Conclusion: Conducting a process evaluation in the pilot phase of an integrated care project can allow adjustments to be made to the project procedures to improve the effectiveness and reproducibility of the intervention going forward.
Bugno, A, Saes, DPS, Almodovar, AAB, Dua, K, Awasthi, R, Ghisleni, DDM, Hirota, MT, de Oliveira, WA & de Jesus Andreoli Pinto, T 2018, 'Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test', Journal of Pharmaceutical Innovation, vol. 13, no. 1, pp. 27-35.
View/Download from: Publisher's site
View description>>
The sterility test described in pharmacopoeial 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 BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.
Chellappan, DK, Hansbro, PM, Dua, K, Hsu, A, Gupta, G, Ng, ZY, Wong, J-Y, Chellian, J & Panneerselvam, J 2018, 'Vesicular Systems Containing Curcumin and Their Applications in Respiratory Disorders – A Mini Review', Pharmaceutical Nanotechnology, vol. 5, no. 4, pp. 250-254.
View/Download from: Publisher's site
View description>>
Vesicular systems like nanotechnology and liposomes are gaining tremendous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance.The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin.We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases.Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on.This mini review, in this direction, tries to highlight the key research interventions employing vesicular systems of drug delivery with curcumin.
Chellappan, DK, Leng, KH, Jia, LJ, Aziz, NABA, Hoong, WC, Qian, YC, Ling, FY, Wei, GS, Ying, T, Chellian, J, Gupta, G & Dua, K 2018, 'The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review', Biomedicine & Pharmacotherapy, vol. 102, pp. 1127-1144.
View/Download from: Publisher's site
View description>>
OBJECTIVE:The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers. METHODS:The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review. RESULTS:In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents. CONCLUSION:Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.
Chellappan, DK, Ng, ZY, Wong, J-Y, Hsu, A, Wark, P, Hansbro, N, Taylor, J, Panneerselvam, J, Madheswaran, T, Gupta, G, Bebawy, M, Hansbro, PM & Dua, K 2018, 'Immunological Axis of Curcumin-Loaded Vesicular Drug Delivery Systems', Future Medicinal Chemistry, vol. 10, no. 8, pp. 839-844.
View/Download from: Publisher's site
View description>>
Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
Chellappan, DK, Sivam, NS, Teoh, KX, Leong, WP, Fui, TZ, Chooi, K, Khoo, N, Yi, FJ, Chellian, J, Cheng, LL, Dahiya, R, Gupta, G, Singhvi, G, Nammi, S, Hansbro, PM & Dua, K 2018, 'Gene therapy and type 1 diabetes mellitus', Biomedicine & Pharmacotherapy, vol. 108, pp. 1188-1200.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Masson SAS Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet β cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors. Methods: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review. Findings: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.
Chellappan, DK, Yap, WS, Bt Ahmad Suhaimi, NA, Gupta, G & Dua, K 2018, 'Current therapies and targets for type 2 diabetes mellitus', Panminerva Medica, vol. 60, no. 3, pp. 117-131.
View/Download from: Publisher's site
View description>>
© 2018 Edizioni Minerva Medica The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharm...
Cutler, RL, Fernandez-Llimos, F, Frommer, M, Benrimoj, C & Garcia-Cardenas, V 2018, 'Economic impact of medication non-adherence by disease groups: a systematic review', BMJ Open, vol. 8, no. 1, pp. e016982-e016982.
View/Download from: Publisher's site
View description>>
ObjectiveTo determine the economic impact of medication non-adherence across multiple disease groups.DesignSystematic review.Evidence reviewA comprehensive literature search was conducted in PubMed and Scopus in September 2017. Studies quantifying the cost of medication non-adherence in relation to economic impact were included. Relevant information was extracted and quality assessed using the Drummond checklist.ResultsSeventy-nine individual studies assessing the cost of medication non-adherence across 14 disease groups were included. Wide-scoping cost variations were reported, with lower levels of adherence generally associated with higher total costs. The annual adjusted disease-specific economic cost of non-adherence per person ranged from $949 to $44 190 (in 2015 US$). Costs attributed to ‘all causes’ non-adherence ranged from $5271 to $52 341. Medication possession ratio was the metric most used to calculate patient adherence, with varying cut-off points defining non-adherence. The main indicators used to measure the cost of non-adherence were total cost or total healthcare cost (83% of studies), pharmacy costs (70%), inpatient costs (46%), outpatient costs (50%), emergency department visit costs (27%), medical costs (29%) and hospitalisation costs (18%). Drummond quality assessment yielded 10 studies of high quality with all studies performing partial economic evaluations to varying extents.ConclusionMedication non-adherence places a significant cost burden on healthcare systems. Current research assessing the economic impact of medication non-adherence is limited and of varying quality, failing to provide adaptable data to influence health policy. The corr...
De Rubis, G, Krishnan, SR & Bebawy, M 2018, 'Circulating tumor DNA – Current state of play and future perspectives', Pharmacological Research, vol. 136, pp. 35-44.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Ltd Cancer management paradigms are shifting towards a personalized approach thanks to the advent of the -omics technologies. Liquid biopsies, consisting in the sampling of blood and other bodily fluids, are emerging as a valid alternative to circulating tumor biomarkers and tumor tissue biopsies for cancer diagnosis, routine monitoring and prognostication. The content of a liquid biopsy is referred to as the “tumor circulome”. Among its components, circulating tumor DNA (ctDNA), including both cell-free and exosome-associated DNA, is the most widely characterized element. ctDNA analysis has a tremendous capability in the diagnostic arena. Its potential has been demonstrated at each level of disease staging and management and supported by a recent FDA approval for companion diagnostic, and the investments being made by pharmaceutical companies in this sector are numerous. The approaches available for ctDNA analysis allow both quantitative and qualitative studies and range from PCR and dPCR-mediated single/multiple gene mutational assessment to whole genome next generation sequencing and methylation mapping. Although the principal object of a liquid biopsy is blood, other body fluids such as urine and saliva show potential as complementary DNA sources for tumor analysis. In this review we provide a synopsis on the state of play of current ctDNA application. We discuss the clinical significance of ctDNA analysis and review the state of the art of technologies being currently developed to this aim. We also discuss the current issues limiting ctDNA application and highlight the promising approaches being developed to overcome these.
de Souza Botelho-Almeida, T, Lourenço, FR, Kikuchi, IS, Awasthi, R, Dua, K & Andreoli Pinto, TDJ 2018, 'Evaluating the Potential, Applicability, and Effectiveness of Ozone Sterilization Process for Medical Devices', Journal of Pharmaceutical Innovation, vol. 13, no. 2, pp. 87-94.
View/Download from: Publisher's site
View description>>
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Purpose: Ozone (O3) can be considered the most potent natural germicide against microorganisms (in vegetative and spore forms) with high efficiency and speed, because of its highly oxidizing activity. Despite this, there are a few studies describing the application of ozone as a sterilizing agent of medical devices. The aim of this communication was to describe the development and validation of a sterilization cycle applied to medical devices. Methods: The sterilization process was challenged using Geobacillus stearothermophilus ATCC 7953 spores, which have shown great resistance. The sterilizing effect of ozone was measured using carriers inoculated with 106 CFU/mL spores, introduced into a 3-mL syringe and lumens of tubes of different sizes and diameters simulating hospital medical products, which have undergone a half-cycle or complete cycle. Results: The results of sterilization process studied in active vegetative form of microorganisms showed that the ozone sterilization was effective with a bioburden between 105 to 107 CFU/mL with one pulse sterilizing action. The validation of the process was confirmed by the satisfactory results for the half-cycle, corresponding to a treatment with four pulses allowed sterilizing the material with bioburdens < 106 CFU/mL spores which indicate an appropriate sterility assurance level. Conclusion: The results showed that the ozone may be considered as effective and promising alternative for sterilization of thermosensitive materials and medical devices.
Dua, K, Bebawy, M, Awasthi, R, Tekade, RK, Tekade, M, Gupta, G, De Jesus Andreoli Pinto, T & Hansbro, PM 2018, 'Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems', Pharmaceutical Nanotechnology, vol. 5, no. 4, pp. 243-249.
View/Download from: Publisher's site
View description>>
The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically.We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose.Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis.This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science.
Dua, K, Hansbro, NG, Foster, PS & Hansbro, PM 2018, 'Targeting MicroRNAs: Promising Future Therapeutics in the Treatment of Allergic Airway Disease', Critical Reviews in Eukaryotic Gene Expression, vol. 28, no. 2, pp. 125-127.
View/Download from: Publisher's site
View description>>
MicroRNAs (miRNAs) are short noncoding RNAs that control gene expression posttranscriptionally by directly blocking translation of their target mRNAs or by repressing protein production via mRNA destabilization. Investigations into miRNAs began approximately 12 years ago with their discovery in mammalian cells. Still, the involvement of miRNAs in the development of asthma remains unclear, and this topic needs further research to discover various molecular mechanisms responsible for the pathogenesis of asthma and new therapeutic interventions. So far, various miRNAs have been identified in allergic airway disease along with their targets. Our present mini-review highlights the latest information involving the role of miRNAs in asthma.
Dua, K, Rapalli, VK, Shukla, SD, Singhvi, G, Shastri, MD, Chellappan, DK, Satija, S, Mehta, M, Gulati, M, Pinto, TDJA, Gupta, G & Hansbro, PM 2018, 'Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches', Biomedicine & Pharmacotherapy, vol. 107, pp. 1218-1229.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Masson SAS Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.
Gadzhanova, S, Roughead, EE & Pont, LG 2018, 'Antidepressant switching patterns in the elderly', International Psychogeriatrics, vol. 30, no. 9, pp. 1365-1374.
View/Download from: Publisher's site
View description>>
ABSTRACTBackground:Switching between antidepressants is complex due to potential adverse outcomes such as serotonin syndrome and antidepressant discontinuation syndrome, yet switching is often required due to non-response to initial treatment. This study aimed to examine the patterns and extent of antidepressant switching in a cohort of older adults in long-term residential care.Methods:A cohort study of medication supply data from 6011 aged care residents in 60 long-term care facilities was conducted. Incident antidepressant users were followed for 12 months and their patterns of antidepressant use determined. The type of switching from and to different antidepressant classes was determined according to National and International recommendations for antidepressant switching.Results:In total, 11% (n= 44) of the residents were initiated on an antidepressant medication (n= 402) switched to a different antidepressant agent within 12 months. Residents commenced on a SNRI or TCA were most likely to switch antidepressants (17% in each group). Almost half of the switches (n= 21, 48% of all switches) were not implemented according to guideline recommendations. Direct switch and taper followed by wash out and switch, accounted for all of the inappropriate switching (29% and 71%, respectfully), with half occurring to mirtazapine (N= 7) or from mirtazapine (N= 3).Conclusions:Over one in 10 long-term aged care residents who commence an antidepressant will switch to a different antidepressant within 12 months. Current antidepressant switching practices in long-term residential aged...
Gupta, G, Bebawy, M, Pinto, TDJA, Chellappan, DK, Mishra, A & Dua, K 2018, 'Role of the Tristetraprolin (Zinc Finger Protein 36 Homolog) Gene in Cancer', Critical Reviews in Eukaryotic Gene Expression, vol. 28, no. 3, pp. 217-221.
View/Download from: Publisher's site
Gupta, G, Chellappan, DK, de Jesus Andreoli Pinto, T, Hansbro, PM, Bebawy, M & Dua, K 2018, 'Tumor suppressor role of miR-503', Panminerva Medica, vol. 60, no. 1, pp. 17-24.
View/Download from: Publisher's site
View description>>
© 2017 EDIZIONI MINERVA MEDICA. MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate posttranscriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR-503, an associate of the 'canonical' miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR-503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR-503 in different cancers and elaborate on its mechanism of action.
Gupta, G, de Jesus Andreoli Pinto, T, Chellappan, DK, Mishra, A, Malipeddi, H & Dua, K 2018, 'A clinical update on metformin and lung cancer in diabetic patients', Panminerva Medica, vol. 60, no. 2, pp. 70-75.
View/Download from: Publisher's site
View description>>
© 2018 EDIZIONI MINERVA MEDICA. diabetes mellitus (dm) is frequently increased in many countries and become a serious health problem worldwide. diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer. (Cite this article as: Gupta G, de Jesus andreoli Pinto T, chellappan dK, mishra a, malipeddi H, dua K. a clinical update on metformin and lung cancer in diabetic patients.
Gupta, G, Sharma, RK, Dahiya, R, Mishra, A, Tiwari, J, Sharma, GN, Sharma, S & Dua, K 2018, 'Aphrodisiac Activity of an Aqueous Extract of Wood Ear Mushroom, Auricularia polytricha (Heterobasidiomycetes), in Male Rats', International Journal of Medicinal Mushrooms, vol. 20, no. 1, pp. 81-88.
View/Download from: Publisher's site
Gupta, G, Singhvi, G, Chellappan, DK, Sharma, S, Mishra, A, Dahiya, R, de Jesus Andreoli Pinto, T & Dua, K 2018, 'Peroxisome proliferator-activated receptor gamma: promising target in glioblastoma', Panminerva Medica, vol. 60, no. 3, pp. 109-116.
View/Download from: Publisher's site
View description>>
Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
Jansen, K, Haugen, DF, Pont, L & Ruths, S 2018, 'Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life—A Systematic Literature Review', Journal of Pain and Symptom Management, vol. 55, no. 2, pp. 508-521.e3.
View/Download from: Publisher's site
View description>>
© 2017 The Authors. Context: Dying patients commonly experience potentially distressing symptoms. Palliative care guidelines recommend opioids, anticholinergics, antipsychotics, and benzodiazepines for symptom relief. Objectives: The objective of this study was to systematically review the effectiveness and safety of palliative drug treatment in the last days of life of adult patients, focusing on the management of pain, dyspnea, anxiety, restlessness, and death rattle. Methods: A systematic search of the literature was published before December 2016 in PubMed/MEDLINE, Embase, CINAHL, PsycINFO, Cochrane, ClinicalTrials.gov, and SveMed+. Studies on safety or effectiveness of drug therapy in dying adults with at least one outcome on symptom control, adverse effects, or survival were included. Data for included studies were extracted. Study quality was assessed using the Effective Public Health Practice Quality assessment tool for quantitative studies. Results: Of the 5940 unique titles identified, 12 studies met the inclusion criteria. Five studies assessed anticholinergics for death rattle, providing no evidence that scopolamine hydrobromide and atropine were superior to placebo. Five studies examined drugs for dyspnea, anxiety, or terminal restlessness, providing some evidence supporting the use of morphine and midazolam. Two studies examined opioids for pain, providing some support for morphine, diamorphine, and fentanyl. Eight studies included safety outcomes, revealing no important differences in adverse effects between the interventions and no evidence for midazolam shortening survival. Conclusion: There is a lack of evidence concerning the effectiveness and safety of palliative drug treatment in dying patients, and the reviewed evidence provides limited guidance for clinicians to assist in a distinct and significant phase of life.
Lucas, C, Williams, K, Tudball, J & Walpola, RL 2018, 'Community, hospital and industry preceptor perceptions of their role in experiential placements- the need for standardization of preceptor responsibilities and evaluations on students', Currents in Pharmacy Teaching and Learning, vol. 10, no. 11, pp. 1447-1455.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Inc. Introduction: Appropriate evaluation processes are important in experiential placements. With the growing diversity between placements, consideration for standardization of some of these processes would be beneficial, particularly for those skills that are transferable regardless of the placement type. The objectives of this study was: (1) to explore the experiences, evaluation strategies, and feedback processes of Australian preceptor pharmacists from three primary experiential areas (community, hospital, and industry) in providing student placements; and (2) to inform the future development of the current local experiential program and future extended international experiential programs. Methods: A qualitative, exploratory study with three preceptor focus groups (community, hospital, and industry) were conducted, recorded, and transcribed verbatim. Data were analyzed using Bazeley's “describe – compare – relate” method for thematic analysis. Results: There were a total of 16 participants. Four themes emerged: (1) motivation and purpose of being a preceptor; (2) expectations of students and the university; (3) organizational planning and conduct of experiential placements; and (4) importance of appropriate evaluation and feedback processes to include evaluation of interpersonal skills, which were considered by all focus group members as highly desirable for future employability. Conclusions: The need for standardized processes across different experiential placements, although difficult given the diversity, is important particularly with respect to evaluation and feedback. As interpersonal attributes are transferable and desirable for all types of experiential settings including rural and international environments, standardizing the evaluation of students to include these could be beneficial and applicable for students on local experiential placements and/or cross globally on international experiential placements.
Lucas, C, Williams, KA, McAloon, J & Walpola, R 2018, 'From expectations to experience: Pharmacy students' perceptions on experiential placements', Research in Social and Administrative Pharmacy, vol. 14, no. 8, pp. e45-e45.
View/Download from: Publisher's site
Madan, JR, Patil, S, Mathure, D, Bahirat, SP & Awasthi, R 2018, 'Improving dissolution profile of poorly water-soluble drug using non-ordered mesoporous silica', Marmara Pharmaceutical Journal, vol. 22, no. 2, pp. 249-258.
View/Download from: Publisher's site
View description>>
The aim of the study was to increase dissolution rate of atorvastatin by the use of mesoporous silica SYLOID® 244 FP. The poorly soluble drug atorvastatin was adsorbed on and/or into SYLOID® 244 FP in the ratios 1:1, 1:1.1.5, 1:2, 1:2.5, 1:3 and 1:3.5 via a wetness impregnation method. The absence of crystalline form and presence of hydrogen bond interaction between atorvastatin and SYLOID® 244 FP is done by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The atorvastatin loaded matrix lacked in the crystalline form of atorvastatin and it showed improvement in the dissolution rate of ATC. The flowability of the atorvastatin loaded matrix powder was evaluated by bulk density, Carr’s index and angle of repose. This matrix was then processed into a tablet by direct compression method. A 3 full factorial design was applied to investigate the combined effect of two formulation variables - volume of ethanol and amount of SYLOID® 244 FP. The tablets were evaluated for hardness, friability, drug content and drug dissolution studies. The solubility of atorvastatin-loaded matrix was increased up to 4.28 times. Atorvastatin tablet prepared from drug-loaded silica may provide a feasible approach for development of an oral formulation for this poorly water-soluble drug. 2
Maheshwari, R, Sharma, P, Tekade, M, Atneriya, U, Dua, K, Hansbro, PM & Tekade, RK 2018, 'Microsponge Embedded Tablets for Sustained Delivery of Nifedipine', Pharmaceutical Nanotechnology, vol. 5, no. 3, pp. 192-202.
View/Download from: Publisher's site
View description>>
Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr).To address the problem, we first prepared nifedipine loaded sustained release microsponges and then formulated tablets for effective clinical application and patient compliance.Preparations of microsponges were carried out using different compositions of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique.The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportions (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40°C and 75% RH.The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.
Malipeddi, RV, Awasthi, R & Dua, K 2018, 'Formulation and evaluationof controlled-release matrix systems of ciprofloxacin', Polymers in Medicine, vol. 47, no. 2, pp. 101-106.
View/Download from: Publisher's site
View description>>
Ciprofloxacin is a broad-spectrum fluoroquinolone antibacterial drug to which most Gram-negative and many Gram-positive bacteria are highly susceptible. Fluoroquinolones are administered repeatedly, twice a day for 5 days, during the course of therapy. Hence, they require repeated administration. Ciprofloxacin qualifies as a drug candidate for a controlled-release drug delivery system.The present work was aimed to develop ciprofloxacin hydrochloride-containing matrix tablets by the wet granulation method.The tablets were prepared using EthocelTM 100 Premium and Eudragit® RS PO (Evonik Laboratory, Mumbai, India) as a rate-controlling polymer. Granular dioctyl phthalate (DCP) was used as a diluent. An isopropyl alcohol and dichloromethane (1:1) mixture was used as a granulating agent. The effect of the formulation variables on tablet performance was examined based on weight variation, hardness, friability, thickness, and drug release profiles. The results suggested that the tablets had good integrity.The tablets were stable for 18 months. Formulation F7 gave a linear release pattern up to 12 h. The release of ciprofloxacin from formulation F7 followed zero-order kinetics. The release mechanism was found to be diffusion-controlled as the Higuchi equation was obeyed.Ciprofloxacin hydrochloride-containing matrix tablets were prepared successfully. The tablets had good integrity and were found stable for 18 months.
Manandhar, B, Paudel, KR, Sharma, B & Karki, R 2018, 'Phytochemical profile and pharmacological activity of Aegle marmelos Linn.', Journal of Integrative Medicine, vol. 16, no. 3, pp. 153-163.
View/Download from: Publisher's site
View description>>
© 2018 Aegle marmelos Linn. (Rutaceae), commonly known as “bael” in Nepal and India, is a valuable medicinal plant and is considered sacred by the Hindus. It is used to cure several diseases in the Indian traditional medicine system of Ayurveda and has had similar uses among many ethnic communities residing in Indian subcontinent for over 5000 years. Its leaves, bark, stem, fruits and seeds have been used for various medicinal purposes. Bael fruits are especially effective in the treatment of chronic diarrhea, dysentery and peptic ulcers, while they are also useful as a laxative and cure for respiratory infections. Scientific studies have validated many of the ethnomedicinal uses of A. marmelos, which include antibacterial, antiviral, antidiarrheal, gastroprotective, anti-ulcerative colitis, hepatoprotective, antidiabetic, cardioprotective and radioprotective effects. Recently, this plant has also received attention as an anticancer agent for the treatment of various types of cancers. Thus, this review focuses on scientific evidence verifying the important pharmacological activity such as antioxidant, antidiabetic, antimicrobial, hepatoprotective, cardioprotective and anticancer activity of A. marmelos.
Mathure, D, R Madan, J, N. Gujar, K, Tupsamundre, A, A. Ranpise, H & Dua, K 2018, 'Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route', Pharmaceutical Nanotechnology, vol. 6, no. 1, pp. 69-78.
View/Download from: Publisher's site
View description>>
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. BACKGROUND: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism.OBJECTIVE: The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel.METHODS: Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6.RESULTS: The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride thr...
Mehta, M, Garg, M, Dua, K & Satija, S 2018, 'Simultaneous HPTLC Densitometric Estimation of KBA and AKBA from Boswellia serrata', Current Analytical Chemistry, vol. 15, no. 1, pp. 84-91.
View/Download from: Publisher's site
View description>>
Background: Boswellic acids (BAs) are extracted from oleo gum of Boswellia serrata andare utilized as potential anti-inflammatory, hypolipidemic, immunomodulatory and antitumor specialists.The present examination was meant to assess KBA and AKBA in Boswellia serrata separate byHigh-Performance Thin Layer Chromatography (HPTLC).Methods:The separation of bioactive compounds was performed utilizing mobile phase glacial aceticacid, n-hexane, ethyl acetate and toluene (0.3: 1: 8: 2) (v/v/v/v) and distinguished at wavelength 254nm. The technique was approved for linearity, precision, accuracy, limit of detection (LOD), limit ofquantification (LOQ), and so forth by International Conference on Harmonization guidelines.Results: The calibration range was observed to be 2- 14 μg/band for both the bioactive compounds.KBA was isolated with an Rf estimation of 0.39 ± 0.02 and AKBA with an Rf estimation of0.42 ± 0.02. The accuracy was seen to be as high as 99.17% and 97.42 for KBA and KBA, respectively.The percentage RSD value for intra-day and between day varieties was under 2%. The system indicatedhigh affectability and specificity.Conclusion: The developed HPTLC method was simple, precise, robust, specific, rapid, and costeffectiveand could be used for quality control analysis and quantification of KBA and AKBA in differentherbal formulations containing the plant species.
Ng, ZY, Wong, J-Y, Panneerselvam, J, Madheswaran, T, Kumar, P, Pillay, V, Hsu, A, Hansbro, N, Bebawy, M, Wark, P, Hansbro, P, Dua, K & Chellappan, DK 2018, 'Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma', Colloids and Surfaces B: Biointerfaces, vol. 172, pp. 51-59.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier B.V. Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and −61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in sign...
Pont, LG, Raban, MZ, Jorgensen, ML, Georgiou, A & Westbrook, JI 2018, 'Leveraging new information technology to monitor medicine use in 71 residential aged care facilities: variation in polypharmacy and antipsychotic use', International Journal for Quality in Health Care, vol. 30, no. 10, pp. 810-816.
View/Download from: Publisher's site
Ranpise, HA, Gujar, KN, Mathure, D, Satpute, PP, Awasthi, R, Dua, K & Madan, JR 2018, 'Skin Targeting of Oxiconazole Nitrate Loaded Nanostructured Lipid- Carrier Gel for Fungal Infections', Pharmaceutical Nanotechnology, vol. 6, no. 3, pp. 192-200.
View/Download from: Publisher's site
View description>>
The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxyconazole nitrate (OCXN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size (PS) and percentage entrapment efficiency (% EE) as dependent variables. The OXZN NLCs were characterized for particle size, particle morphology and entrapment efficiency. The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. Hence, OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.
Rapalli, VK, Singhvi, G, Dubey, SK, Gupta, G, Chellappan, DK & Dua, K 2018, 'Emerging landscape in psoriasis management: From topical application to targeting biomolecules', Biomedicine & Pharmacotherapy, vol. 106, pp. 707-713.
View/Download from: Publisher's site
View description>>
Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
Sezgin, G, Georgiou, A, Hardie, R-A, Li, L, Pont, LG, Badrick, T, Franco, GS, Westbrook, JI, Rinehart, N, McLeod, A, Pearce, C, Shearer, M, Whyte, R & Deveny, E 2018, 'Compliance with pathology testing guidelines in Australian general practice: protocol for a secondary analysis of electronic health record data', BMJ Open, vol. 8, no. 11, pp. e024223-e024223.
View/Download from: Publisher's site
View description>>
IntroductionIn Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key part of diagnosis and monitoring. However overutilisationand underutilisation of pathology tests have been reported across several tests and conditions, despite evidence-based guidelines outlining best practice in pathology testing. There are a limited number of studies evaluating the impact of these guidelines on pathology testing in general practice. The aim of our quantitative observational study is to define how pathology tests are used in general practice and investigate how test ordering practices align with evidence-based pathology guidelines.Methods and analysisAccess to non-identifiable patient data will be obtained through electronic health records from general practices across three primary health networks in Victoria, Australia. Numbers and characteristics of patients, general practices, encounters, pathology tests and problems managed over time will be described. Overall rates of encounters and tests, alongside more detailed investigation between subcategories (encounter year, patient’s age, gender, and location and general practice size), will also be undertaken. To evaluate how general practitioner test ordering coincides with evidence-based guidelines, five key candidate indicators will be investigated: full blood counts for patients on clozapine medication; international normalised ratio measurements for patients on warfarin medication; glycated haemoglobin testing for monitoring patients with diabetes; vitamin D testing; and thyroid function testing.Ethics and disseminationEthics clearance to collect data from general practice facilities has be...
Shastri, MD, Shukla, SD, Chong, WC, Dua, K, Peterson, GM, Patel, RP, Hansbro, PM, Eri, R & O’Toole, RF 2018, 'Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis', Oxidative Medicine and Cellular Longevity, vol. 2018, no. 1, pp. 1-10.
View/Download from: Publisher's site
View description>>
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR‐TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first‐/second‐line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S‐oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug‐susceptible and drug‐resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host’s OS response.
Singh, Y, Gupta, G, Sharma, R, Matta, Y, Mishra, A, Pinto, TDJA & Dua, K 2018, 'Embarking Effect of ACE2-Angiotensin 1–7/Mas Receptor Axis in Benign Prostate Hyperplasia', Critical Reviews in Eukaryotic Gene Expression, vol. 28, no. 2, pp. 115-124.
View/Download from: Publisher's site
Singhvi, G, Girdhar, V, Patil, S, Gupta, G, Hansbro, PM & Dua, K 2018, 'Microbiome as therapeutics in vesicular delivery', Biomedicine & Pharmacotherapy, vol. 104, pp. 738-741.
View/Download from: Publisher's site
View description>>
© 2018 Elsevier Masson SAS Microbiome refers to an ecological community of various symbiotic and pathogenic microorganisms, which plays a crucial role in human health and disease. The concept of novel drug delivery systems particularly the vesicular drug delivery systems is gaining massive attention. This emerging technology has started expanding its horizons in the area of microbiome delivery. This mini-review highlights the role of vesicular systems such as nanoparticles, liposomes etc. as a host/carrier for the microbiome in targeting various diseases. This review will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of vesicular delivery system as carrier for microbiome delivery.
Singhvi, G, Manchanda, P, Krishna Rapalli, V, Kumar Dubey, S, Gupta, G & Dua, K 2018, 'MicroRNAs as biological regulators in skin disorders', Biomedicine & Pharmacotherapy, vol. 108, pp. 996-1004.
View/Download from: Publisher's site
Sunkara, KP, Gupta, G, Hansbro, PM, Dua, K & Bebawy, M 2018, 'Functional relevance of SATB1 in immune regulation and tumorigenesis', Biomedicine & Pharmacotherapy, vol. 104, pp. 87-93.
View/Download from: Publisher's site
View description>>
© 2018 The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proliferation and apoptosis through effects on gene expression. SATB1 undergoes various post-translational modifications, which determine its interaction with co-activators and co-repressors to induce regulation of gene transcription. SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers. This paper provides a review on SATB1-mediated immune responses and on its target genes in the context of tumorigenesis and tumour progression. Specifically, we discuss the role of SATB1 in tumour immunity, Epithelial to Mesenchymal Transition (EMT), metastasis and multidrug resistance. Therapeutic targeting of aberrant SATB1 may be an important strategy in the treatment of cancer.
Sureka, S, Gupta, G, Agarwal, M, Mishra, A, K. Singh, S, P. Singh, R, Sah, SK, de Jesus A. Pinto, T & Dua, K 2018, 'Formulation, In-Vitro and Ex-Vivo Evaluation of Tretinoin Loaded Cubosomal Gel for the Treatment of Acne', Recent Patents on Drug Delivery & Formulation, vol. 12, no. 2, pp. 121-129.
View/Download from: Publisher's site
View description>>
The current work was attempted to formulate and evaluate the topical sustained release delivery systems called cubosomes containing Tretinoin for the acne treatment. The recent patents on various formulations of tretinoin (EP0408370A2) helped in selecting a new formulation and evaluation.Tretinoin loaded cubosomes were prepared by bottom-up technique, using varying the concentration of lipid and surfactant and keeping the drug concentration constant, a total of nine formulations of tretinoin was developed. These preparations were evaluated for surface charge, particle size, particle morphology, encapsulation efficiency, in-vivo and in-vitro release studies of gel enriched with cubosome dispersion. Finally, the stability studies of cubosomal gel were performed on optimized formulations.Significant result were obtained with tretinoin formulation as the drug is lipophilic, so it gives more depot effect on the epidermis and good retention property. The data obtained from the formulations showed that formulation TCF-5 was the optimized formulation which exhibited better drug release and entrapment efficiency.It can be concluded that cubosomes offer benefits of quick onset as well as the maximal release of drug with fewer side effects. Thus, cubosomes represent a capable transporter having the property to sustain the release of drug, potential to localize the drug in the skin with a possible clinical application for acne vulgaris treatment due to cubosome depot effect on the epidermis.
Tiwari, J, Gupta, G, de Jesus Andreoli Pinto, T, Sharma, R, Pabreja, K, Matta, Y, Arora, N, Mishra, A, Sharma, R & Dua, K 2018, 'Role of microRNAs (miRNAs) in the pathophysiology of diabetes mellitus', Panminerva Medica, vol. 60, no. 1, pp. 25-28.
View/Download from: Publisher's site
View description>>
Diabetes mellitus is becoming the critical problem among the entire world and it is difficult to understand the molecular mechanism representing the concept of diabetic pathology. Recently the knowledge of the involvement of genetics in type 2 diabetes mellitus (T2DM) susceptibility has sketched a great concentration towards the transcriptional activity of β cells within the pancreas. This disease becomes the leading cause of death, so it is necessary to study the molecular pathogenesis, phenotypes, and characteristics to design the therapeutic parameters. Here in this review role of miRNA is being illustrated as it plays a crucial role in the pathogenesis, progression, and fate of beta cells of pancreas regulating the insulin secretion. Here in this review, we try to include the effects and pathophysiology of various miRNA in diabetes mellitus and on the various sites of the human body.
van der Meer, HG, Taxis, K & Pont, LG 2018, 'Changes in Prescribing Symptomatic and Preventive Medications in the Last Year of Life in Older Nursing Home Residents', Frontiers in Pharmacology, vol. 8, no. JAN.
View/Download from: Publisher's site
View description>>
© 2018 van der Meer, Taxis and Pont. Background: At the end of life goals of care change from disease prevention to symptomatic control, however, little is known about the patterns of medication prescribing at this stage. Objectives: To explore changes in prescribing of symptomatic and preventive medication in the last year of life in older nursing home residents. Methods: A retrospective cohort study was conducted using pharmacy medication supply data of 553 residents from 16 nursing home facilities around Sydney, Australia. Residents received 24-h nursing care, were aged = 65 years, died between June 2008 and June 2010 and were using at least one medication 1 year before death. Medications were classified as symptomatic, preventive, or other. A linear mixed model was used to compare changes in prescribing in the last year of life. Results: 68.1% of residents were female, mean age was 88.0 (SD: 7.5) years and residents used a mean of 9.1 (SD: 4.1) medications 1 year before death. The mean number of symptomatic medications per resident increased from 4.6 medications 1 year before death to 5.1 medications at death [95% CI 4.4-4.7 to 5.9-5.2, P = 0.000], while preventive medication decreased from 2.0 to 1.4 medications [95% CI 1.9-2.1 to 1.3-1.5, P = 0.000] . Symptomatic medications were used longer in the last year of life, compared to preventive medications (336.3 days [95% CI 331.8-340.8] versus 310.9 days [95% CI 305.2-316.7] , P = 0.000). Conclusion: Use of medications for symptom relief increased throughout the last year of life, while medications for prevention of long-term complications decreased. But changes were slight and clinical relevance can be questioned.
van der Meer, HG, Wouters, H, Pont, LG & Taxis, K 2018, 'Reducing the anticholinergic and sedative load in older patients on polypharmacy by pharmacist-led medication review: a randomised controlled trial', BMJ Open, vol. 8, no. 7, pp. e019042-e019042.
View/Download from: Publisher's site
View description>>
ObjectiveTo evaluate if a pharmacist-led medication review is effective at reducing the anticholinergic/sedative load, as measured by the Drug Burden Index (DBI).DesignRandomised controlled single blind trial.Setting15 community pharmacies in the Northern Netherlands.Participants157 community-dwelling patients aged ≥65 years who used ≥5 medicines for ≥3 months, including at least one psycholeptic/psychoanaleptic medication and who had a DBI≥1.InterventionA medication review by the community pharmacist in collaboration with the patient’s general practitioner and patient.Primary and secondary outcomes measuresThe primary outcome was the proportion of patients whose DBI decreased by at least 0.5. Secondary outcomes were the presence of anticholinergic/sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission and mortality. Data were collected at baseline and 3 months follow-up.ResultsMean participant age was 75.7 (SD, 6.9) years in the intervention arm and 76.6 (SD, 6.7) years in the control arm, the majority were female (respectively 69.3% and 72.0%). Logistic regression analysis showed no difference in the proportion of patients with a≥0.5 decrease in DBI between intervention arm (17.3%) and control arm (15.9%), (OR 1.04, CI 0.47 to 2.64, p=0.927). Intervention patients scored higher on the Digit Symbol Substitution Test, measure of cognitive function (OR 2.02, CI 1.11 to 3.67, p=0.021) and reported fewer sedative side effects (OR 0.61, CI 0.40 to 0.94, p=0.024) at follow-up. No signifi...
Yeung, S, Traini, D, Lewis, D & Young, PM 2018, 'Dosing challenges in respiratory therapies', International Journal of Pharmaceutics, vol. 548, no. 1, pp. 659-671.
View/Download from: Publisher's site
Yeung, S, Traini, D, Tweedie, A, Lewis, D, Church, T & Young, PM 2018, 'Limitations of high dose carrier based formulations', International Journal of Pharmaceutics, vol. 544, no. 1, pp. 141-152.
View/Download from: Publisher's site
