Box–Behnken Optimization of Rosuvastain-Curcumin Co-Loaded Nanoparticles for Synergistic Anti-Atherosclerotic Therapy

The present study reports the formulation and optimization of poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-encapsulating rosuvastatin and curcumin for synergistic anti-atherosclerotic therapy. A Box–Behnken statistical design was employed to investigate the effects of polymer concentration, polymer-to-drug ratio, and stirring speed on key responses-particle size, zeta potential, entrapment efficiency (EE%), and in-vitro drug release. The optimized formulation exhibited a mean particle size of 155 ± 4 nm, zeta potential of –30 mV, and EE% of 80.1 ± 1.5%, demonstrating excellent colloidal stability and controlled release. In-vitro studies revealed a biphasic release pattern best described by the Higuchi model (R² > 0.98), confirming diffusion-controlled kinetics. The co-loaded nanoparticles enhanced intestinal permeability ex-vivo and produced a synergistic anti-inflammatory response in RAW 264.7 macrophages (Combination Index = 0.58). The non-covalent hybrid nanocomplex improved compatibility between rosuvastatin and curcumin, achieving sustained release and enhanced bioavailability. Overall, the optimized PLGA nanocarrier provides a promising dual-drug delivery platform for controlled and synergistic management of atherosclerosis.