Engineered Clay-Polymer Composite for Biomedical Drug Delivery and Future Challenges: A Survey.

Clay materials are widely used in drug delivery systems due to their unique characteristics. Montmorillonite is a major component of bentonite and it has a large surface area, better swelling capacity, and high adsorption capacity. The modification of natural bentonite could improve its sorption ability for new emerging applications. Recent advancements in the polymer-silicate composite have novel biomedical applications in drug delivery, tissue regeneration, wound healing, cancer therapy, enzyme immobilization, diagnostic and therapeutic devices, etc. Perspective view of the montmorillonite- polymer composite as a pharmaceutical carrier in drug delivery systems has been discussed in this review. Different types of modification of montmorillonite for the development of pharmaceutical formulations have also been documented. Many challenges in clay nanocomposite systems of polymer of natural/synthetic origin are yet to be explored in improving antimicrobial properties, mechanical strength, stimuli responsiveness, resistance to hydrolysis, etc. Drug interaction and binding capability, swelling of clay may be carried out for finding possible applications in monitoring delivery systems. Pharmaceutical properties of active drugs in the formulation could also be improved along with dissolution rate, solubility, and adsorption. The clay-incorporated polymeric drug delivery systems may be examined for a possible increase in swelling capacity and residence time after mucosal administration.

Drug repurposing a compelling cancer strategy with bottomless opportunities: Recent advancements in computational methods and molecular mechanisms.

Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment. This review gathered about how in silico drug repurposing offers the opportunity to quickly increase the anticancer drug arsenal and, more importantly, overcome some of the limits of existing cancer therapies against both old and new therapeutic targets in oncology. The ancient nononcology compounds' innovative potential targets and important signaling pathways in cancer therapy are also discussed. This review also includes many plant-derived chemical compounds that have shown potential anticancer properties in recent years. Here, we have also tried to bring the spotlight on the new mechanisms to support clinical research, which may become increasingly essential in the future; at the same time, the unsolved or failed clinical trial study should be reinvestigated further based on the techniques and information provided. These encouraging findings, combined together, will through new insight on repurposing more non-oncology drugs for the treatment of cancer.

DNA Methylation Profiling of Ovarian Tissue of Climbing Perch (Anabas testudienus) in Response to Monocrotophos Exposure.

Epigenetic modifications like DNA methylation can alter an organism's phenotype without changing its DNA sequence. Exposure to environmental toxicants has the potential to change the resilience of aquatic species. However, little information is available on the dynamics of DNA methylation in fish gonadal tissues in response to organophosphates. In the present work, reduced-representation bisulfite sequencing was performed to identify DNA methylation patterns in the ovarian tissues of Anabas testudienus exposed to organophosphates, specifically monocrotophos (MCP). Through sequencing, an average of 41,087 methylated cytosine sites were identified and distributed in different parts of genes, i.e., in transcription start sites (TSS), promoters, exons, etc. A total of 1058 and 1329 differentially methylated regions (DMRs) were detected as hyper-methylated and hypo-methylated in ovarian tissues, respectively. Utilizing whole-genome data of the climbing perch, the DMRs, and their associated overlapping genes revealed a total of 22 genes within exons, 45 genes at transcription start sites (TSS), and 218 genes in intergenic regions. Through gene ontology analysis, a total of 16 GO terms particularly involved in ovarian follicular development, response to oxidative stress, oocyte maturation, and multicellular organismal response to stress associated with reproductive biology were identified. After functional enrichment analysis, relevant DMGs such as steroid hormone biosynthesis (Cyp19a, 11-beta-HSD, 17-beta-HSD), hormone receptors (ar, esrrga), steroid metabolism (StAR), progesterone-mediated oocyte maturation (igf1ar, pgr), associated with ovarian development in climbing perch showed significant differential methylation patterns. The differentially methylated genes (DMGs) were subjected to analysis using real-time PCR, which demonstrated altered gene expression levels. This study revealed a molecular-level alteration in genes associated with ovarian development in response to chemical exposure. This work provides evidence for understanding the relationship between DNA methylation and gene regulation in response to chemicals that affect the reproductive fitness of aquatic animals.

Ocular delivery of felodipine for the management of intraocular pressure and inflammation: Effect of film plasticizer and in vitro in vivo evaluation.

Glaucoma may cause irreversible eyesight loss and damage to the optic nerve. Trabecular meshwork obstruction may raise intraocular pressure (IOP) in open-angle and/or closed-angle type inflammatory glaucoma. Ocular delivery of felodipine (FEL) has been undertaken for the management of intraocular pressure and inflammation. FEL film was formulated using different plasticizers, and IOP has been assessed using a normotensive rabbit eye model. Ocular acute inflammation induced by carrageenan has also been monitored. Drug release has been enhanced significantly (93.9 % in 7 h) in the presence of DMSO (FDM) as a plasticizer in the film compared to others (59.8 to 86.2 % in 7 h). The same film also exhibited the highest ocular permeation of 75.5 % rather than others (50.5 to 61.0 %) in 7 h. Decreased IOP was maintained up to 8 h after ocular application of FDM compared to the solution of FEL only up to 5 h. Ocular inflammation has almost been disappeared within 2 h of using the film (FDM), whereas inflammation has been continued even after 3 h of the induced rabbit without film. DMSO plasticized felodipine film could be used for the better management of IOP and associated inflammation.

Modeling of chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: An approach for better management of atherosclerosis.

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation. To enhance the therapeutic efficacy and physical properties of AT and CU, a new conjugate derivative (AT-CU) was synthesized and assessed by in silico, in vitro characterizations, and in vivo efficacy through mice model. Although the biocompatibility and biodegradability of Polylactic-co-Glycolic Acid (PLGA) in nanoparticles are well documented, burst release is a common issue with this polymer. Hence the current work used chitosan as a drug release modifier to the PLGA nanoparticles. The chitosan-modified PLGA AT-CU nanoparticles were prepaid by single emulsion and solvent evaporation technique. With raising the concentration of chitosan the particle size grew from 139.2 nm to 197.7 nm, the zeta potential rose from -20.57 mV to 28.32 mV, and the drug encapsulation efficiency improved from 71.81% to 90.57%. At 18 h, the burst release of AT-CU from PLGA nanoparticles was seen, hitting abruptly 70.8%. For chitosan-modified PLGA nanoparticles, the burst release pattern was significantly reduced which could be due to the adsorption of the drug on the surface of chitosan. The efficiency of the ideal formulation i.e F4 (chitosan/PLGA = 0.4) in treating atherosclerosis was further strongly evidenced by in vivo investigation.

Bentonite-in hypromellose-poloxamer sol-gel for corneal application of trimetazidine: Study of rheology and ocular anti inflammatory potential.

Bentonite is reported to be used for extending ocular drug delivery safely in a controlled manner. Bentonite combined hydroxypropyl methylcellulose (HPMC)-poloxamer based sol-to-gel formulation has been developed for the prophylactic ocular anti-inflammatory effect of trimetazidine after corneal application. HPMC-poloxamer sol formulation was prepared incorporating trimetazidine to bentonite at 1: 2*10-5 to 1:5*10-6 ratios using cold method, and investigations were carried out in carrageenan-induced rabbit eye model. Pseudoplastic shear thinning behavior without any yield value and high viscosity at low shear rate were the positive attribute of the tolerability of the sol formulation after ocular instillation. Presence of bentonite nanoplatelets revealed more sustained in vitro release (~79-97 %) and corneal permeation (~79-83 %) over a period of 6 h in comparison to its absence. Prominent acute inflammation has been produced in the carrageenan-induced untreated eye, whereas the absence of ocular inflammation has been noticed in the previously sol-treated eye even after carrageenan injection. HPMC-poloxamer-based formulation exhibited stronger binding affinity (5.13 kcal/mol) in the presence of bentonite rather than its absence (3.99 kcal/mol), resulting in a stable and sustained effect. HPMC-poloxamer in-situ gel of trimetazidine containing bentonite could be utilized for sustained ocular delivery and the control of ophthalmic inflammation prophylactically.

The burden & contributing factors of psychological distress across India during the COVID pandemic.

The unprecedented COVID-19 pandemic spread rapidly and engulfing the entire world, forcing people to stay home, muting the hustle and bustle of modern world with tide of fear for contracting disease and death. This brutal disease has infected millions of people worldwide, many lost their job, world economies have ravaged and many more uncountable consequences. OBJECTIVE: To assess the psychological distress due to COVID-19 outbreak and to determine contributing factors towards psychological distress. METHOD: A cross-sectional survey was conducted between 12th May to 20th June 2020 & 1537 valid responses were received. Modified K10 scale was used to assess psychological distress. Binary logistic regression analysis was used to determine extent of relationship between the contributing factors and psychological distress scale by estimating the odds of having significant stress with P ≤ 0.05. RESULT: A total of 1537 valid responses were obtained. The overall psychological distress score was 19.79 ± .75 which implies mild psychological distress. Analysis of degree of psychological distress revealed 815 (53.0%) with no psychological distress, 385 (25.0%) mild, 194 (12.6%) moderate and 143 respondents (9.3%) had severe degree of psychological distress. Females psychological distress was 1.448 times as compared to male (CI 0.191-10.986). The odds of having significant psychological distress for above 60 years as compared to 16-30 years. Shop owner & business man had more stress in compared to professionals (OR 1.176, CI 0.058-2.362). As compared to married, the psychological distress was 13.203 times higher among divorcee/separated (0.786-221.787) and 3.629 times higher among unmarried (0.376-35.054). CONCLUSION: This study showed 39.2% of the subject had psychological distress which is quite high. So, government and other policy makers have to develop strategy to relieve psychological distress among Indian population.

Design, synthesis and molecular modeling studies of novel mesalamine linked coumarin for treatment of inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are continuous idiopathic inflammation of GIT. Ulcerative colitis, inflammation of the colonic or rectal mucosa has no known medical cure and its treatment is aimed at reducing the signs and symptoms associated with the disorders, induction and maintenance of remission. In this study, we have reported the synthesis of mesalamine and coumarin linked together by a diazo group. The compound was characterized by various spectroscopic methods. Therapeutic potential of the synthesized compound was investigated through acetic acid induced ulcerative rat model. Pharmacokinetic properties were predicted for the compounds by ADMET related descriptors. Molecular docking studies were conducted with four proteins (COX-2, MMP-9, TNF-α and MPO) to examine the interaction of mesalamine (MS) and mesalamine coumarin derivative (MS-CU). Moreover, molecular dynamic simulations were carried out to study the dynamics and stability of the complexes in solvent system. The binding energy of MS-CU with MPO, COX-2, MMP-9 and TNF-α was found to be -9.5, -10.4, -9.2 and -8.4 kcal/mol respectively. MS-CU exhibited higher binding affinity towards all tested proteins than MS. Molecular dynamic simulation reveals that both MS and MS-CU formed a stable complex with all test proteins in aqueous system. Overall binding energy of MS-CU was more than MS showing stronger affinity towards the test portions. In conclusion, Mesalamine-coumarin derivative reduces colonic damage in acetic acid induced ulcerative colitis in rat model, and therefore may prove to be effective in the management of IBD.