Pravara Rural College of Pharmacy

To develop and optimize zavegepant-loaded mucoadhesive microemulsions for intranasal delivery, utilizing quality-by-design principles for enhanced bioavailability and rapid onset in acute migraine management. Zavegepant-loaded microemulsions were formulated using Labrafil M 1944 CS (oil), Brij 35 (surfactant), polyethylene glycol (PEG) 400 (co-surfactant), gellan gum (mucoadhesive polymer), and double distilled water. A central composite design with 4 factors (oil, surfactant, co-surfactant, and water concentrations) was employed to optimize critical quality attributes including globule size, zeta potential, and polydispersity index. Comprehensive characterization included particle size analysis, surface charge determination, drug content, permeation studies, and accelerated stability testing. Twenty-seven formulations were evaluated, with statistical analysis identifying concentration as the primary determinant of microemulsion properties (F-values: 144.64-375.27). Optimization yielded formulation (10% Labrafil M 1944 CS, 52% Brij 35, 18% PEG 400, 20% water) with ideal characteristics: globule size 58.7 nm, Polydispersity index 0.142, zeta potential -12.7± mV, and drug content 99.6. It demonstrated superior ex-vivo drug permeation (91.7% at 12h) and remained stable for 6 months under accelerated conditions. The optimized mucoadhesive microemulsion showed good in vitro results with fast drug release, strong permeation, and stable performance. This suggests it could be a useful intranasal system for zavegepant in treating migraines, but in vivo studies are still needed to confirm its clinical use.

Objectives: This study aimed to develop and optimize tivozanib-loaded amine-functionalized mesoporous silica nanoparticles (AF-MSNs) to enhance solubility, drug loading, and enhanced delivery for renal cell carcinoma therapy. Methods: Tivozanib was loaded into MCM-41 and MCM-41 silica carriers using solvent impregnation, and initial batches were screened for encapsulation efficiency, particle size, zeta potential, and solubility. A Box-Behnken factorial design was employed to optimize DETAS concentration, reaction time, and temperature for effective amine functionalization. Characterization was performed via FTIR, DSC, UV, and in vitro release studies. Cell viability was evaluated using MTT assay on A498 renal cell carcinoma cells. Results: MCM-41 with a 1:2 drug-to-silica ratio showed the best performance with an encapsulation efficiency of 85.2 %, solubility of 68.4 & micro;g/mL, and particle size of 175 nm. Optimization using Box-Behnken design identified SF14 as the best batch, exhibiting amine content of 2.52 mmol/g, zeta potential + 35.8 mV, and drug loading of 78.4 %. In vitro release showed sustained drug release of 78.42 % over 12 h. The dose-response analysis revealed IC50 values of 18.4 +/- 1.2 mu g/mL for the optimized silica formulation, 25.2 +/- 1.8 mu g/mL for pure tivozanib, and 31.7 +/- 2.1 mu g/mL for sorafenib standard. Statistical analysis showed significant differences between all groups (one-way ANOVA, F (2,6) = 28.45, p = 0.0008). The optimized formulation demonstrated significantly lower IC50 compared to pure tivozanib (p = 0.012) and sorafenib (p = 0.0003), while pure tivozanib showed significantly lower IC50 than sorafenib (p = 0.024). The positive control doxorubicin showed an IC50 of 2.8 +/- 0.4 mu g/mL, confirming assay sensitivity. Empty AF-MSNs demonstrated minimal cytotoxicity with > 85 % cell viability at the highest tested concentration (200 mu g/mL), indicating that the observed cytotoxic effects were primarily due to the loaded drug rather than the carrier system. The optimized batch remained stable over 6 months under ICH conditions with no significant changes in critical parameters. Conclusion: The optimized AF-MSN formulation significantly improved the physicochemical properties, enhanced anticancer efficacy, and sustained release profile of tivozanib, supporting its potential to enhance clinical efficacy and reduce systemic toxicity. These findings indicate strong promise for future in vivo studies and potential clinical translation in targeted cancer therapy.

Biological weapons are a serious threat to global health and can cause widespread illness and disruption. This review looks at how these weapons affect human health by focusing on important biological agents, how they spread, and their symptoms. We discuss key agents like anthrax and smallpox, which can lead to severe health issues. We explain the ways these agents can be transmitted, such as through the air, ingestion, or insects, and describe the symptoms people may experience. The review also covers the psychological effects of biological attacks, including stress and social stigma, as well as the economic impacts, like job loss and pressure on healthcare systems. Finally, we highlight the challenges in responding to biological threats, such as the need for better detection, vaccines, and preparedness plans. Understanding the effects of biological weapons is crucial for creating effective strategies to protect individuals and communities.

Euphorbia neriifolia, a plant with diverse traditional medicinal uses, exhibits various pharmacological activities, including analgesic, anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, and immunomodulatory effects. Its phytochemical constituents, such as triterpenoids, flavonoids, saponins, and alkaloids, contribute to these properties. Traditionally, it's used to treat wounds, skin conditions, digestive issues, and respiratory problems. However, caution is necessary due to potential toxicity and skin irritation. Consultation with a healthcare professional is recommended before using Euphorbia neriifolia for medicinal purposes.

Tafenoquine (TF), a quinoline-derived antimalarial compound, had been utilized both as a chemoprophylactic agent and in combination therapies such as with artesunate. Despite its potent efficacy against Plasmodium falciparum, its clinical application had been restricted due to reports of neurotoxicity and adverse neuropsychiatric reactions. Previous computational investigations indicated that TF functioned as a dual cholinesterase inhibitor with a high affinity for protein targets, findings that were subsequently corroborated through in vitro enzymatic inhibition studies. Malaria continued to represent a significant global health challenge, particularly within tropical and subtropical regions, owing to the emergence of Plasmodium falciparum and Plasmodium vivax strains resistant to conventional antimalarial drugs. Targeting essential parasitic enzymes, including aspartic proteases, had been recognized as a promising strategy for discovering novel chemotherapeutic candidates. In the present study, an in silico molecular docking approach was employed to examine a series of Tafenoquine analogues as potential inhibitors of critical Plasmodium proteins. Among the fourteen designed derivatives, TF4A, TF8A, TF3A, and TF1A exhibited stronger binding affinities than the parent compound Tafenoquine, with docking energies of −8.1, −8.5, −8.0, and −8.2 kcal/mol, respectively. Additionally, ADMET evaluation and drug-likeness analyses demonstrated that these analogues possessed acceptable pharmacokinetic characteristics and conformed to Lipinski’s rule of five, suggesting good oral bioavailability and favorable physicochemical behavior. Collectively, the computational findings indicated that halogen-substituted Tafenoquine analogues, particularly TF8A and TF1A, established stable interactions within the catalytic pockets of target proteins and exhibited enhanced binding energies. Therefore, these derivatives could be considered as promising lead scaffolds for future antimalarial drug development. Nevertheless, further in vitro and in vivo investigations would be necessary to validate their efficacy, metabolic stability, and safety profiles.