High Antitumor Activity of the Dual Topoisomerase Inhibitor P8-D6 in Breast Cancer

Breast cancer constitutes the leading cause of cancer deaths among females. However, numerous shortcomings, including low bioavailability, resistance and significant side effects, are responsible for insufficient treatment. The ultimate goal, therefore, is to improve the success rates and, thus, the range available treatment options for breast cancer. Consequently, the identification, development and evaluation of potential novel drugs such as P8-D6 with seminal antitumor capacities have a high clinical need. P8-D6 effectively induces apoptosis by acting as a dual topoisomerase I/II inhibitor. This study provides an overview of the effectiveness of P8-D6 in breast cancer with both 2D monolayers and 3D spheroids compared to standard therapeutic agents. For this drug effectiveness review, cell lines and ex vivo primary cells were used and cytotoxicity, apoptosis rates and membrane integrity were examined. This study provides evidence for a significant P8-D6-induced increase in apoptosis and cytotoxicity in breast cancer cells compared to the efficacy of standard therapeutic drugs. To sum up, P8-D6 is a fast and powerful inductor of apoptosis and might become a new and suitable therapeutic option for breast cancer in the future.

Design and Fabrication of a New MHD Micropump for Continuous Subcutaneous Infusion to Thalassemia Major Patients

Background: In recent decades, reducing the size of the drug delivery systems along with precise control of the amount of drug pumped, has attracted the attention of many researchers. Objectives: The slow subcutaneous infusion of the deferoxamine in thalassemia major patients during day is of vital importance either for the drug effectiveness. However, this is difficult to achieve due to the large size of the conventional infusion pumps and their high weight. Therefore, size and weight reduction of the infusion pumps are very important issues that must be well addressed. Methods: A biomedical micropump for drug solution infusion to human body based on the magnetohydrodynamic (MHD) concept is and designed, and its performance experimentally is investigated in this research. The key challenge in the fabrication of the micropump is its size, weight, bubble generation, and high operating voltage. Results: The present design is well responded to these problems. The final design operates with a 1.2 v without any bubble generation, while its size and weight are 20 × 40 × 50 mm3 and 90 grams, respectively. The size of the micropump is about 1/3 size of conventional micropump, while its weight is half of them. Conclusions: Therefore, the newly designed micropump has the ability to inject the drug solution to thalassemia major patients with a sufficient infusion rate during the day without disturbing them, so it can increase their quality of life and increase their life expectancy.

Innate Immunity Modulating Impurities and the Immunotoxicity of Nanobiotechnology-Based Drug Products

Innate immunity can be triggered by the presence of microbial antigens and other contaminants inadvertently introduced during the manufacture and purification of bionanopharmaceutical products. Activation of these innate immune responses, including cytokine secretion, complement, and immune cell activation, can result in unexpected and undesirable host immune responses. These innate modulators can also potentially stimulate the activation of adaptive immune responses, including the formation of anti-drug antibodies which can impact drug effectiveness. To prevent induction of these adverse responses, it is important to detect and quantify levels of these innate immunity modulating impurities (IIMIs) that may be present in drug products. However, while it is universally agreed that removal of IIMIs from drug products is crucial for patient safety and to prevent long-term immunogenicity, there is no single assay capable of directly detecting all potential IIMIs or indirectly quantifying downstream biomarkers. Additionally, there is a lack of agreement as to which of the many analytical assays currently employed should be standardized for general IIMI screening. Herein, we review the available literature to highlight cellular and molecular mechanisms underlying IIMI-mediated inflammation and its relevance to the safety and efficacy of pharmaceutical products. We further discuss methodologies used for direct and indirect IIMI identification and quantification.

Formulation and Evaluation of Nanosuspension as an Alternative Approach for Solubility Enhancement of Simvastatin

Solubility is an essential factor for drug effectiveness. Simvastatin is poorly water-soluble drug and its bioavailability is very low. Nanosuspension is one of those approach which can tremendously enhance the effective surface area of drug particles by reducing the particle size and there by increases the rate of dissolution and hence improve bioavailability. The main purpose of the present investigation was to increase the saturation solubility of simvastatin by preparation of nanosuspension. Nanosuspension of simvastatin were prepared by nanoprecipitation method using hydroxypropyl cellulose as stabilizer and sodium lauryl sulphate as surfactant. Prepared nanosuspension was evaluated for its particle size, total drug content, entrapment efficiency and saturation solubility study. On the basis of the evaluation, the best batch F8 formulation demonstrated highest drug content and entrapment efficiency with average particle size of 0.004µm. The saturation solubility studies show the solubility of the prepared nanosuspension has increased as compared to the pure drug due to the particle size reduction. The nanosuspension of simvastatin could be successfully prepared and can be concluded that the nanosuspension formulation is a promising approach to enhance the solubility. The nanoprecipitation is a simple and effective method to produce nano sized particles of poorly water-soluble drugs with enhance solubility.

Analysing and reporting of observational data: a systematic review informing the EULAR points to consider when analysing and reporting comparative effectiveness research with observational data in rheumatology

ObjectivesTo evaluate the analysis and reporting of comparative effectiveness research with observational data in rheumatology, informing European Alliance of Associations for Rheumatology points to consider.MethodsWe performed a systematic literature review searching Ovid MEDLINE for original articles comparing drug effectiveness in longitudinal observational studies, published in key rheumatology journals between 2008 and 2019. The extracted information focused on reporting and types of analyses. We evaluated if year of publication impacted results.ResultsFrom 9969 abstracts reviewed, 211 articles fulfilled the inclusion criteria. Ten per cent of studies did not adjust for confounding factors. Some studies did not explain how they chose covariates for adjustment (9%), used bivariate screening (21%) and/or stepwise selection procedures (18%). Only 33% studies reported the number of patients lost to follow-up and 25% acknowledged attrition (drop-out or treatment cessation). To account for attrition, studies used non-responder imputation, followed by last observation carried forward (LOCF) and complete case (CC) analyses. Most studies did not report the number of missing data on covariates (83%), and when addressed, 49% used CC and 11% LOCF. Date of publication did not influence the results.ConclusionMost studies did not acknowledge missing data and attrition, and a tenth did not adjust for any confounding factors. When attempting to account for them, several studies used methods which potentially increase bias (LOCF, CC analysis, bivariate screening…). This study shows that there is no improvement over the last decade, highlighting the need for recommendations for the assessment and reporting of comparative drug effectiveness in observational data in rheumatology.