Bioresponsive Chitosan-PVA Hydrogels Encapsulating Ginsenosides-Rich Panax ginseng for Triple Action Therapeutics: Integrating Smart Drug Release with Anti-Cancer, Anti-Diabetic and Wound Healing Applications

Abstract

The integration of natural phytochemicals into advanced biomaterials presents a transformative approach to managing complex chronic diseases. In this study, we developed a multifunctional, biodegradable hydrogel composed of chitosan and polyvinyl alcohol (PVA), encapsulating Panax ginseng extract, and evaluated its in vitro therapeutic potential across five biomedical domains anticancer, antioxidant, anti-inflammatory, antidiabetic, and wound healing. SEM analyses confirmed successful ginsenoside incorporation, revealing a porous, bioactive matrix suitable for sustained release. The hydrogel exhibited potent cytotoxicity against HT-29 colon cancer cells, achieving an IC₅₀ of 25 µg/mL and inducing apoptosis. The MTT assay revealed a marked decrease in HT-29 cell viability at 25 µg/ml concentration of chitosan-PVA hydrogel containing Panax ginseng, with viability reduced to 48.3 ± 1.6%, indicating significant anticancer potential at this dose. Strong radical scavenging (78% DPPH inhibition) and protein stabilization (70% inhibition in egg albumin denaturation assay) demonstrated its dual oxidative and inflammatory suppression. The hydrogel also inhibited α-amylase and α-glucosidase by up to 75%, confirming metabolic regulatory potential. A biphasic release profile delivered nearly 100% cumulative release within 48 hours. Most notably, in a wound scratch assay using Danio rerio gill cells, the hydrogel achieved complete wound closure within 42 hours significantly faster than the 72-hour healing observed in comparable systems highlighting its regenerative efficacy. Compared to hydrogels loaded with honey or synthetic agents, our P. ginseng-based formulation demonstrated superior multifunctionality and biocompatibility. These results establish this smart hydrogel as a robust platform for integrated chronic disease management and regenerative medicine.