DEVELOPMENT AND BIOCHEMICAL EVALUATION OF A NOVEL BIOPOLYMER-BASED DRUG DELIVERY SYSTEM FOR ENHANCED THERAPEUTIC EFFICACY

Abstract

Biopolymer-based nanocarriers offer a promising strategy for improving drug stability, controlled release, and intracellular therapeutic delivery. This study developed and computationally evaluated a chitosan-alginate nanoparticle system for doxorubicin delivery using a dataset encompassing formulation, drug-release, biochemical efficacy, and stability parameters. Among 120 candidate formulations, F110 achieved the highest composite desirability (0.7879), with a particle size of 209 nm, polydispersity index of 0.252, encapsulation efficiency of 86.5%, drug loading of 19.1%, and production yield of 96.0%. Multivariable analysis identified drug-to-polymer ratio, chitosan, and alginate as major determinants of formulation performance. Nanoparticle incorporation prolonged the time to 50% drug release from 0.650 h for free doxorubicin to 3.301 h at pH 5.5 and 6.632 h at pH 7.4. Full release profiles followed first-order kinetics, while early nanoparticle release showed anomalous/non-Fickian behavior. Loaded nanoparticles demonstrated enhanced cellular uptake, reactive oxygen species generation, caspase-3 activity, and greater reductions in cell viability at selected doses. Refrigerated storage better preserved physicochemical stability over 90 days. Overall, the optimized system demonstrated favorable formulation, controlled-release, biochemical, and stability characteristics, supporting further experimental validation for advanced drug-delivery applications.