Transfersomes: A Novel Vesicular Carrier for Enhanced Transdermal Delivery of Sertraline: Development,Characterization, and Performance Evaluation

The aim of the present study was to investigate transfersomes as a transdermal delivery system for the poorly soluble drug, sertraline, in order to overcome the troubles associated with its oral delivery. Different transfersomal formulations were prepared with non-ionic surfactant (span 80), soya lecithin, and carbopol 940 by the rotary evaporation sonication method. The prepared formulations were characterized for light microscopy, particle size analysis, drug entrapment, turbidity, drug content, rheological studies, in vitro release, ex vivo permeation, and stability studies. The optimized formulation was evaluated for in vivo studies using the modified forced swim model test. FTIR studies showed compatibility of the drug with excipients. The result revealed that sertraline in all of the formulations was successfully entrapped with uniform drug content. Transfersomal gel containing 1.6% of the drug and 20% of span 80 was concluded to be the optimized formulation (EL-SP4), as it showed maximum drug entrapment (90.4±0.15%) and cumulative percent drug release(73.8%). The ex vivo permeation profile of EL-SP4 was compared with the transfersomal suspension, control gel, and drug solution. The transfersomal gel showed a significantly higher (p<0.05) cumulative amount of drug permeation and flux along with lower lag time than the drug solution and drug gel. It also owed to better applicability due to the higher viscosity imparted by the gel rather than the transfersomal suspension, and no skin irritation was observed. The modified forced swim test in mice revealed that the transfersomal gel had better antidepressant activity as compared to the control gel. Thus, the study substantiated that the transfersomal gel can be used as a feasible alternative to the conventional formulations of sertraline with advanced permeation characteristics for transdermal application.     

Block Copolymer Synthesis via a Combination of ATRP and RAFT Using Click Chemistry

Block copolymer synthesis via a combination of ATRP and RAFT using click chemistry is reported for the first time. A RAFT agent with a terminal propargyl group (PTTC) was synthesized and was used to polymerize butyl acrylate and gave quantitative monomer conversion. Azide‐terminated p(tbA) was obtained by ATRP followed by reaction with sodium azide. Later, using CuBr‐PMDETA as catalyst via click chemistry, p(tBA)_(ATRP) and p(BA)_(RAFT) were reacted to get a block copolymer of p(tBA)_(ATRP)‐b‐p(BA)_(RAFT). Further, a total of 24 block copolymers were made by reacting four azido functional polymers with six propargyl functional polymers to obtain block copolymers via click chemistry.

     

Risk factors of type 2 diabetes in population of Jammu and Kashmir,India

We sought to identify risk factors for type 2 diabetes (T2D) in Jammu and Kashmir populations, India. A total of 424 diabetic and 226 non-diabetic subjects from Jammu, and 161 diabetic and 100 non-diabetic subjects from Kashmir were screened for various parameters including fasting blood glucose level, 2 hour glucose level, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL-C), uric acid, systolic and diastolic blood pressure level. We found that subjects aged 40-49 years had the highest rate of diabetes, with family income playing not much of a role. Kashmiri migrants or populations with rapid cultural, environmental, social or lifestyle change along with reduced physical activity, obesity and unhealthy lifestyle (smoking and alcohol consumption) were found to have higher rates of diabetes. High blood glucose, triglycerides and low HDL-C levels were found to be contributing to disease outcome. High blood pressure also contributed to a higher risk of developing T2D. Our study supports earlier reports confirming the contribution of comfortable life style, Western dietary habits and rapid life style change along with many other factors to the prevalence of diabetes. This may contribute to the epidemic proportion of diabetes in Jammu and Kashmir. Early diagnosis and routine screening for undiagnosed diabetes in obese subjects and subjects with parental diabetes history is expected to decrease the burden of chronic diabetic complications worldwide.     

Hydroxyurea in Sickle Cell Disease: Our Experience in Western India

Sickle cell disease (SCD) is common in tribal belt of Gujarat, but not addressed effectively as it should be with effective use of Hydroxyurea, supportive care and counseling. In our single centre study of 70 patients of SCD who were only on Folic acid and Blood transfusion support, were analyzed and followed up for 1 year in terms of their clinical symptoms, Blood transfusion requirement, laboratory parameters before and after Hydroxyurea therapy. We found statistically significant improvement in clinical symptoms and positive changes in laboratory parameters studied. This validates the well established role of Hydroxyurea in SCD as seen in the various international trials. Hence it is imperative that the well documented benefits of Hydroxyurea in various International studies should be translated into clinical practice. SCD should be treated like a chronic disorder needing preventive therapy in form of Hydroxyurea and counseling with regular follow up.     

Non-invasive delivery of nanoparticles to hair follicles: A perspective for transcutaneous immunization

Transfollicular vaccination aims to reach the peri-follicular antigen presenting cells without impairing the stratum corneum (SC) barrier. This would be an optimal vaccination strategy under critical hygienic conditions. Nanoparticles (NPs) are the ideal vehicles for transfollicular delivery of vaccines as they are able to (i) penetrate deeper into the hair follicles than molecules in solution, (ii) can help to stabilize protein based antigen and (iii) improve and modulate the immune response.     

Chromosomal structural variations during progression of a prostate epithelial cell line to a malignant metastatic state inactivate the NF2, NIPSNAP1, UGT2B17, and LPIN2 genes

Prostate cancer is the second highest cause of male cancer deaths in the United States. A significant number of tumors advance to a highly invasive and metastatic stage, which is typically resistant to traditional cancer therapeutics. In order to identify chromosomal structural variants that may contribute to prostate cancer progression we sequenced the genomes of a HPV-18 immortalized nonmalignant human prostate epithelial cell line, RWPE1, and compared it to its malignant, metastatic derivative, WPE1-NB26. There were a total of 34 large (>1 Mbp) and 38 small copy number variants (<100 kbp) in WPE1-NB26 that were not present in the precursor cell line. We also identified and validated 46 structural variants present in the two cell lines, of which 23 were unique to WPE1-NB26. Structural variants unique to the malignant cell line inactivated: (1) the neurofibromin2 (NF2) gene, a known tumor suppressor; (2) its neighboring gene NIPSNAP1, another putative tumor suppressor that inhibits TRPV6, an anti-apoptotic oncogene implicated in prostate cancer progression; (3) UGT2B17, a gene that inactivates dihydrotestosterone, a known activator of prostate cancer progression; and (4) LPIN2, a phosphatidic acid phosphatase and a co-factor of PGC1a that is important for lipid metabolism and for suppressing autoinflammation. Our results illustrate the value of comparing the genomes of defined related pairs of cell lines to discover chromosomal structural variants that may contribute to cancer progression.     

Dietary Phenolic Acids of Macrotyloma uniflorum (Horse Gram) Protect the Rat Heart Against Isoproterenol‐Induced Myocardial Infarction

The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p‐coumaric acid and ferulic acid) in isoproterenol (ISO)‐induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO‐elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C‐reactive protein and malondialdehyde and a restoration of the levels of the ISO‐depleted marker enzymes, reduced glutathione and the antioxidant enzymes—superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO‐altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO‐challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd.