Bombay College of Pharmacy

Inhibition of carbohydrate digesting enzymes like pancreatic α-amylase has proven to be an effective strategy in countering postprandial hyperglycaemia. However, unwanted adverse effects associated with current therapies, such as ACB, voglibose, and miglitol, have necessitated the development of safer and more effective alternatives. These challenges have prompted growing interest in natural product scaffolds, particularly phenolic compounds, which exhibit favourable safety profiles and multifaceted enzyme inhibition. In this context, the strategic design of molecular conjugates integrating bioactive phenolics offers a promising route to enhance inhibitory potency, binding specificity, and therapeutic relevance. Reportedly, molecular hybrids with chalcone, phenolic acid, coumarin and polyphenol backbone exhibited impressive antioxidant and potent inhibition against digestive enzymes. In the quest of developing novel anti-hyperglycaemic agents, we report in vitro and in silico evaluation of the novel TPAC as potential pancreatic α-amylase inhibitors in the present work. Among the ten conjugates, T5 (IC50 = 50.65 ± 0.76 µM) exhibited strong inhibition against PPA which was comparable to positive control ACB (24.81 ± 0.98 µM). Computational binding analysis revealed binding of T5 to HPA (PDB ID: 2QV4) by interacting with the amino acid residues and distorting the receptor's catalytic site conformation. Furthermore, the conformational dynamic studies and electron density driven simulations established the stability and high reactivity of T5 within the ligand-receptor complex. The in silico studies corroborated the in vitro enzyme inhibition results, reinforcing the mechanistic insights into ligand-receptor interactions. Taken together, the experimental and computational results indicate that T5 merits further investigation as a candidate molecule targeting pancreatic α-amylase for the management of T2D .

Dasatinib (DAS) exhibits therapeutic potential for the treatment of lung cancer. However, its clinical utility is marred owing to poor solubility, low oral bioavailability, and rapid systemic clearance. Therefore, the current investigation is aimed to develop and optimize a polymeric nanoparticulate delivery system for DAS to increase its physicochemical properties and anticancer potential. Herein, pullulan was used as a stabilizer and encapsulating agent because of its biocompatibility and structural flexibility, allowing for effective DAS entrapment and controlled release. DAS-loaded nanoparticles were optimized employing a Box-Behnken design. The formulation was characterized for particle size, entrapment efficiency (% EE), zeta potential, invitro drug release, and cytotoxicity against A549 lung cancer cells. The optimized formulation exhibited the particle size of 135.3 nm, EE of 92.8 %, and a zeta potential of-7.9 mV. FTIR and DSC analyses confirmed no significant drug-excipient incompatibility and corroborated successful drug encapsulation. The invitro release studies demonstrated sustained release of DAS over 48 h at pH7.4 (71.84±3.12 %) and 6.8 (84.65±4.10 %). DAS-loaded nanoparticles exhibited significantly higher cytotoxicity (65.49 %) compared to plain DAS (42.23 %). Overall, a pullulan-based nanoparticulate system offers a promising technique for improving DAS delivery and therapeutic efficacy in lung cancer treatment.

Glioblastoma multiforme (GBM) is responsible for about half of all primary malignant tumors in the central nervous system (CNS). Nanotechnology and nanocarrier-based drug delivery may prove to be an asset in the ongoing fight against the difficulties associated with treating GBM. Obstacles to effective drug delivery in GBM treatment include prolonged blood circulation, sufficient BBB transit, effective internalization, and controlled drug release within GBM cells. By virtue of the non-specific and non-targeted character of anti-tumor medicines, the efficiency of medication delivery to gliomas is still impoverished. Glioma diagnosis and therapy have undergone a paradigm change solely because of nanotechnology. The highly invasive nature of this malignant glioma makes surgical resection a challenging procedure, and the current approved standard of care—follow-up radiation therapy with concurrent temozolomide (TMZ)—will only prolong the lifespan of patients by a few months. Drug delivery nanosystems (DDNSs) have garnered attention in the treatment of cancer, particularly gastrointestinal cancer, according to recent studies. This is because DDNPs have proven to be effective substitutes for conventional formulations currently on the market, in addition to optimizing the delivery of drugs to neoplastic cells, ameliorating the profile of toxicity and unfavorable effects, and reducing the overall harmful effects of formulations that include antineoplastic agents. Specifically, nanocarriers have proven to have an exceptional ability to get over the difficulties to achieve drug accumulation in the brain without going through the system delivering by IN route. Pre-clinical research on polymeric nanocarriers for treating GBM is ongoing, with few drug delivery systems entering clinical trials. This study examines nanoparticle forms, and brain tumor statistics, and summaries the diagnosis and treatment of GBM utilizing nanotechnology.

Till now, 642 million COVID-19 cases have been confirmed, claiming around 6.62 million lives. The impact of SARS-CoV-2 on the male reproductive system, both short and long-term, remains a mystery. This study aims to scrutinize how SARS-CoV-2 affects sexual function, considering potential mediators such as psychological stress. Results reveal that the infection intensifies metabolic stress, directly or indirectly impacting male fertility and causing psychological distress with heightened ROS generation. The exclusive presence of Angiotensin-converting enzyme 2 (ACE2) in type II pneumocytes, serving as the virus receptor, suggests lungs as the primary target. In conclusion, SARS-CoV-2 infection potentially diminishes male fertility, primarily due to psychological stress, raising concerns about COVID-19-induced male infertility amid other factors. Despite limited therapeutic options for COVID-19 and ongoing vaccine efforts, the persistent threat of diverse strains poses a long-term risk to global population health.

In this work, a UV spectrophotometric approach that is accurate, precise, and environmentally friendly Is proposed for concurrent quantification of Ritonavir and Nirmatrelvir in combination pharmaceutical form. While treating COVID-19, these antiviral medications are essential. The Q-absorbance method was created and validated in accordance with ICH criteria, and the simultaneous estimation method is constructed utilizing two distinct solvents. After being evaluated for linearity, accuracy, precision, robustness, and sensitivity, the suggested techniques showed great reproducibility and high correlation coefficients (r2 = 0.999). One-way ANOVA statistical comparison verified that the devised methodologies were reliable and consistent for pharmaceutical analysis, with no significant differences found.Furthermore, the Green Analytical Procedure Index (GAPI), AGREE, and BAGI criteria were used to assess the Ecological sustainability of these methods. The results demonstrated that the suggested approaches provide a greener substitute for traditional analytical procedures by drastically lowering solvent usage and the production of hazardous waste. The proposed UV spectrophotometric approaches offer a straightforward, economical, and dependable solution for the routine quality evaluation of Ritonavir and Nirmatrelvir in dosage forms.

ABSTRACT: A simple approach was developed for the rapid, selective and sensitive estimation of finerenone in spiked human plasma utilizing the high-performance liquid chromatography (HPLC) method. The protein precipitation technique was adopted for sample preparation, subsequently followed by separation and detection using the HPLC system. The quantification of finerenone in spiked human plasma was validated in compliance with regulatory guidelines (USFDA, EMEA and ICH). A mixture consisting of acetonitrile and water was utilized as the mobile phase. The separation was accomplished using a Phenomenex C18 column. The concentration range achieved was from 150 ng/ml to 6000 ng/ml. The accuracy obtained was 95 to 103% for calibration standards and 92 to 102 % for quality control (QC) samples. The precision was < 4% and recovery study showed 88% recovery. The stability study was conducted and the proposed method was determined to be stable. The application of one-way ANOVA revealed no significant variability in intra- and inter-day precision (p > 0.05), thereby confirming the consistency of the method. The method was effectively developed and validated, demonstrating simplicity, accuracy, rapidity, sensitivity and cost effectiveness.