Poluri Koteswari

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor with limited therapeutic options, largely due to poor drug penetration across the blood–brain barrier (BBB). Capecitabine, a prodrug of 5-fluorouracil, has demonstrated potential against glioblastoma; however, its short half-life and limited brain delivery may restrict its therapeutic efficacy. This study aimed to develop and evaluate a thermoresponsive intranasal nanoemulsion-based in situ gel of capecitabine for potential nose-to-brain delivery in GBM therapy. Capecitabine-loaded nanoemulsion in situ gels were prepared using triolein, egg lecithin, and Pluronic F127 and F68 by emulsification followed by probe sonication. The formulations were evaluated for physicochemical characteristics, drug content, thermal compatibility, morphology, and in vitro drug release. The optimized formulation (F5) exhibited a gelation temperature of 33.2 ± 0.45 °C and a pH of 6.4, indicating suitability for intranasal administration. F5 showed an average droplet size of 219.7 nm, polydispersity index of 0.12, and zeta potential of −16.6 mV, indicating a uniform and stable nanoemulsion system. The drug content was 97.67 ± 1.564%. Differential scanning calorimetry confirmed compatibility between capecitabine and the formulation excipients, while scanning electron microscopy revealed spherical lipid droplets dispersed within the gel matrix. The optimized formulation demonstrated sustained drug release, achieving 99.64 ± 0.119% cumulative release over 8 h. Drug release kinetics followed the Higuchi and Korsmeyer–Peppas models, suggesting diffusion-controlled release. Overall, the developed thermoresponsive intranasal nanoemulsion-based in situ gel demonstrates promising physicochemical and drug-release characteristics for potential nose-to-brain delivery of capecitabine in glioblastoma therapy.

Curcumin is a novel phytochemical compound proven to be effective in treating many types of cancers, including skin cancer. But its therapeutic applications are limited due to its poor aqueous solubility, stability, and permeability. Methods: To overcome these problems, a novel non-aqueous gel formulation loaded with curcumin was developed for topical administration, using Versagel as the gel base, and its ex vivo permeability characteristics were evaluated. Results: The formulations showed a good spreadability, with 18.6% and 23-40% of the drug released within 24 hours of ex vivo studies. The drug release data were fitted to the Higuchi model and the Korsmeyer-Peppas model. The rate of drug release followed first-order kinetics, and the mechanism of drug release was found to be pure Fickian diffusion. Stability studies revealed that curcumin was stable at room temperature, with a calculated half-life of 1506 days. No skin irritation was observed in the skin irritation test. Conclusion: It is concluded that for drugs unstable in aqueous physiological environments, with poor permeability and oral bioavailability, incorporating them into a non-aqueous topical gel (Versagel) represents a novel approach to enhance their stability and therapeutic efficacy in skin cancers.