High-Expansion Natural Composite Films for Controlled Delivery of Hydroxycitric Acid in Obesity Therapy

Expandable films represent a promising gastroretentive drug delivery system, offering prolonged gastric retention and sustained drug release features particularly advantageous for obesity treatment. This study developed high-expansion films using konjac and various low glycemic index starches, including purple potato, brown rice, resistant, and red jasmine rice starches, in combination with chitosan and hydroxypropyl methylcellulose (HPMC) E15. Garcinia extract was incorporated into the films using the solvent casting technique. Among 27 formulations, all demonstrated rapid unfolding (within 15 min) and significant expansion (2-4 folds). Hydroxycitric acid (HCA), the active component, was encapsulated at efficiencies exceeding 80% <i>w</i>/<i>w</i>. The konjac-based films exhibited favorable mechanical properties, expansion capacity, and drug content uniformity. Notably, the CK3-H1 formulation (2% <i>w</i>/<i>v</i> chitosan, 3% <i>w</i>/<i>v</i> konjac, 1% <i>w</i>/<i>v</i> HPMC E15) provided sustained HCA release over 8 h via diffusion. Cytotoxicity tests showed no toxic effects on RAW 264.7 macrophages at concentrations up to 400 μg/mL. Furthermore, CK3-H1 achieved notable nitric oxide inhibition (35.80 ± 1.21%) and the highest reduction in lipid accumulation (31.09 ± 3.15%) in 3T3-L1 adipocytes, outperforming pure HCA and garcinia extract. These results suggest that expandable konjac-based films are a viable and effective delivery system for herbal anti-obesity agents.