Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline.

Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention.

Solid Self-Nanoemulsifying Drug Delivery Systems of Furosemide: In Vivo Proof of Concept for Enhanced Predictable Therapeutic Response.

Liquid self-nano emulsifying drug delivery systems (SNEDDS) of furosemide (FSM) have been explored as a potential solution for enhancing solubility and permeability but are associated with rapid emulsification, spontaneous drug release, and poor in vivo correlation. To overcome the shortcoming, this study aimed to develop liquid and solid self-emulsifying drug delivery systems for FSM, compare formulation dynamics, continue in vivo therapeutic efficacy, and investigate the advantages of solidification. For this purpose, liquid SNEDDS (L-SEDDS-FSM) were formed using oleic acid as an oil, chremophore EL, Tween 80, Tween 20 as a surfactant, and PEG 400 as a co-surfactant containing 53 mg/mL FSM. At the same time, solid SNEDDS (S-SEDDS-FSM) was developed by adsorbing liquid SNEDDS onto microcrystalline cellulose in a 1:1 ratio. Both formulations were evaluated for size, zeta potential, lipase degradation, and drug release. Moreover, in vivo diuretic studies regarding urine volume were carried out in mice to investigate the therapeutic responses of liquid and solid SNEDDS formulations. After dilution, L-SEDDS-FSM showed a mean droplet size of 115 ± 4.5 nm, while S-SEDDS-FSM depicted 116 ± 2.6 nm and zeta potentials of -5.4 ± 0.55 and -6.22 ± 1.2, respectively. S-SEDDS-FSM showed 1.8-fold reduced degradation by lipase enzymes in comparison to L-SEDDS-FSM. S-SEDDS-FSM demonstrated a sustained drug release pattern, releasing 63% of the drug over 180 min, in contrast to L-SEDDS-FSM, exhibiting 90% spontaneous drug release within 30 min. L-SEDDS-FSM exhibited a rapid upsurge in urine output (1550 ± 56 µL) compared to S-SEDDS-FSM, showing gradual urine output (969 ± 29 µL) till the 4th h of the study, providing sustained urine output yet a predictable therapeutic response. The solidification of SNEDDS effectively addresses challenges associated with spontaneous drug release and precipitation observed in liquid SNEDDS, highlighting the potential benefits of solid SNEDDS in improving the therapeutic response of furosemide.

Assessment of the scope, completeness, and consistency of various drug information resources related to COVID-19 medications in pregnancy and lactation.

BACKGROUND: Drug use in pregnancy and lactation is challenging. It becomes more challenging in pregnant and lactating women with certain critical clinical conditions such as COVID-19, because of inconsistent drug safety data. Therefore, we aimed to evaluate the various drug information resources for the scope, completeness, and consistency of the information related to COVID-19 medications in pregnancy and lactation. METHODS: Data related to COVID-19 medications from various drug information resources such as text references, subscription databases, and free online tools were used for the comparison. The congregated data were analyzed for scope, completeness, and consistency. RESULTS: Scope scores were highest for Portable Electronic Physician Information Database (PEPID), Up-to-date, and drugs.com compared to other resources. The overall completeness scores were higher for Micromedex and drugs.com (p < 0.05 compared to all other resources). The inter-reliability analysis for overall components by Fleiss kappa among all the resources was found to be 'slight' (k < 0.20, p < 0.0001). The information related to the older drugs in most of the resources, provides in-depth details on various components such as pregnancy safety, clinical data related to lactation, the effect of the drug distribution into breast milk, reproductive potential/infertility risk and the pregnancy category/recommendations. However, the information related to these components for newer drugs was superficial and incomplete, with insufficient data and inconclusive evidence, which is a statistically significant observation. The strength of observer agreement for the various COVID-19 medications ranged from poor to fair and moderate for the various recommendation categories studied. CONCLUSION: This study reports discrepancies in the information related to pregnancy, lactation, drug level, reproductive risk, and pregnancy recommendations among the resources directing to refer to more than one resource for information about the safe and quality use of medications in this special population.The present study also emphasizes the need for development of comprehensive, evidence-based, and precise information guide that can promote safe and effective drug use in this special population.

Effect of Polymers and Permeation Enhancers in the Release of Quetiapine Fumarate Transdermal Patch through the Dialysis Membrane.

Quetiapine Fumarate is potent, and the daily therapeutic dose can be delivered easily across the skin with the help of permeation enhancers. Quetiapine Fumarate-loaded transdermal patches were prepared by solvent evaporation technique. Various formulation parameters, excipients, and their combinations were optimized to get thin, translucent, smooth, stable, and high permeable character patches. A total number of 10 formulations were prepared. All formulations were subjected to various physicochemical evaluations. Three different formulations were prepared and F1, F2, and F3. Various physicochemical studies were carried out and found no significant difference between the three batches. The in vitro release study showed 74.29%, 82.73%, and 77.27%, respectively, up to 24 h. From the results, F2 has been selected as an optimized formulation and evaluated for skin irritation test. The results revealed that there is no irritation produced. The stability study results showed that there is no significant change from its initial nature till the period of three months in both temperatures. Quetiapine Fumarate Transdermal Patch F2 has achieved the goal of extended-release, cost-effectiveness, lowering the dose and frequency of drug administration, and thus may improve patient compliance.

The Effect of Polymers on Drug Release Kinetics in Nanoemulsion In Situ Gel Formulation.

Glaucoma is an ocular condition characterized by elevated intraocular pressure (IOP). Conventional treatments of glaucoma face poor corneal permeability and bioavailability. To address these issues, a nanoemulsion in situ gel of Timolol maleate was developed in this study by adding the polymer Carbopol 934p. Using Carbopol 934p, a novel ophthalmic pH-induced nanoemulsion in situ gel was formulated. The formulation was liquid at pH 4 and quickly gelled when the pH was raised to 7.4 (Lacrimal pH). The pH-triggered in situ gelling mechanism demonstrated continuous drug release over a 24 h cycle. A total of nine trial formulations were prepared (NEI1-NEI9) and subjected to various physicochemical and in vitro evaluations. According to the in vitro release kinetics, the drug release of Timolol maleate nanoemulsion in situ gel NEI5 followed zero-order kinetics, with a release exponent value of 0.902, indicating that the mechanism of release was non-Fickian diffusion regulated. In vivo results showed that Timolol maleate nanoemulsion in situ gel NEI5 provided a better-sustained release of the drug, compared with the Timolet OD eye drops. The formulation is stable in storage, with no distinguishable change in appearance, physical properties, quality, and percentage drug release. NEI5 also reduces drug administration frequency, which improves patient compliance. Timolol maleate nanoemulsion in situ gel NEI5 achieved the goal of controlled drug delivery with extended-release and cost-effectiveness, lowering the dosage and frequency of drug administration, and thus may improve patient compliance. In conclusion, the stable nanoemulsion in situ gel of Timolol maleate NEI5 decreases intraocular pressure (IOP) over a prolonged period.

Potential Psychotropic and COVID-19 Drug Interactions: A Comparison of Integrated Evidence From Six Database Programs.

Background Drug interactions are a significant issue in mental illnesses and coronavirus disease 2019 (COVID-19) infections. Inconsistency in drug interaction resources makes prescribing challenging for healthcare professionals. To assess the scope, completeness, and consistency of drug-drug interactions (DDIs) between psychotropic and COVID-19 medications in six specific drug information (DI) databases. Methodology For the comparison, six DI resources were used: Portable Electronic Physician Information Database, Micromedex®, Medscape.com, UpToDate®, Drugs.com drug interaction checker, and WebMD.com drug interaction checker. Using the Statistical Package for the Social Sciences (SPSS) software version 27 (IBM Corp., Armonk, NY), the gathered data were examined for scope, completeness, and consistency. Results Scope scores were higher for PEPID© than all the other resources (p < 0.001) for each comparison. PEPID© had better overall completeness scores (median 5, Interquartile range [IQR] 5 to 5; p<0.05 for each comparison), except for Drugs.com (p < 0.05 for each comparison), and were more remarkable for Micromedex® (median 5, IQR 5 to 5). The Fleiss kappa scores among the six different DI sources were poor (k < 0.20, p < 0.05) for the category of information related to clinical effects and level of documentation, moderate agreement (k = 0.4 - 0.6, p < 0.05) for the severity and course of action of DDIs, and fair agreement (k = 0.4 - 0.6, p < 0.05) for mechanism. Conclusion A comprehensive, accurate information among DI resources is essential for healthcare professionals that will significantly impact patient care in the clinical practice. Banking on high-quality resources will help healthcare professionals to make an informed decision while prescribing to avoid inappropriate combinations that can adversely affect patient outcomes.

Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus.

Resveratrol is a naturally occurring polyphenolic compound. Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus (DM). We hypothesized, therefore, that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus (T2DM). The present clinical study was therefore carried out to test the hypothesis. Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital, Ootacamund, India, in a prospective, open-label, randomized, controlled trial. Patients were randomized into control and intervention groups. The control group received only oral hypoglycemic agents, whereas the intervention group received resveratrol (250 mg/d) along with their oral hypoglycemic agents for a period of 3 months. Hemoglobin A(1c), lipid profile, urea nitrogen, creatinine, and protein were measured at the baseline and at the end of 3 months. The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c) (means ± SD, 9.99 ± 1.50 vs 9.65 ± 1.54; P < .05), systolic blood pressure (mean ± SD, 139.71 ± 16.10 vs 127.92 ± 15.37; P < .05), total cholesterol (mean ± SD, 4.70 ± 0.90 vs 4.33 ± 0.76; P < .05), and total protein (mean ± SD, 75.6 ± 4.6 vs 72.3 ± 6.2; P < .05) in T2DM. No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed. Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes.