544. Box-Behnken design based optimization of polyvinylpyrrolidone stabilized valproic acid nanoemulsion and evaluation of its anticancer potential
Namita Hegde, Kapil Juvale, Sachin Puri, Aditi Chavan, Shivani Shah, ColloidPolymersSci, (2024), DOI: 10.1007/s00396-024-05283-6
Marketed valproic acid formulations use its solid salt forms, which are hygroscopic and difficult to handle. The current study focuses on developing valproic acid nanoemulsion using the physically most stable liquid form of the drug and evaluating its anticancer potential. Valproic acid is a histone deacetylase inhibitor having anticancer potential. The valproic acid nanoemulsion was formulated using a facile and scalable homogenization process. The emulsion stabilization was achieved through viscosity-enhancing polymer polyvinylpyrrolidone K-30 and tween 80. The formulation was optimized using the Box-Behnken model of design of experiments and was evaluated for efficacy and safety in cancer and fibroblast cell lines, respectively. The optimized emulsion showed particle size below 150 nm, polydispersity index below 0.3, zeta potential near − 8.5 mV, density 0.9923 g/cm3, viscosity 2.06 poise, creaming index below 20, drug content 100.37%w/v and acceptable stability at accelerated environmental conditions. Overall, under all the studied conditions of in vitro dissolution and ex vivo permeability, drug release from emulsion was found better than the free drug and comparable to the marketed solution of sodium valproate. The cytotoxicity studies demonstrated improved IC50 values for breast and lung cancer cell lines, with selectivity for cancer cells. The valproic acid nanoemulsion was prepared using its physically stable liquid form. The combination of polymer polyvinylpyrrolidone K-30 and tween 80 demonstrated the desired stabilization of the dispersed phase of the emulsion. The formulated nanoemulsion effectively potentiated valproic acid’s anticancer activity in cell culture assays.