Development and evaluation of insulin-loaded chitosan nanoparticles incorporated into HPMC/PVA topical film for diabetic wound management

Abstract

Introduction Chronic diabetic wounds, particularly foot ulcers, exhibit delayed healing due to impaired tissue repair and infection risk. Topical insulin has shown wound-healing benefits, while nanotechnology-based carriers such as chitosan nanoparticles embedded in polymeric films can enable sustained and localized delivery to enhance therapeutic outcomes. Methods Insulin-loaded chitosan nanoparticles were prepared by ionic gelation using sodium tripolyphosphate (TPP). Eight formulations (F1–F8) were developed and evaluated for particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Four optimized nanoparticle batches (F1–F4) were incorporated into hydroxypropyl methylcellulose (HPMC)/polyvinyl alcohol (PVA) films. The films were assessed for mechanical properties, surface pH, drug content, and in vitro insulin release using dialysis and Franz diffusion cell techniques. Release kinetics were analysed using established mathematical models. Results Optimized nanoparticles showed a mean particle size of 129 nm, a PDI of 0.139, a zeta potential of + 16.27 mV, and encapsulation efficiency of 80–95%. The selected film (F4) exhibited good mechanical integrity (>100 folding cycles), skin-compatible pH (6.57), and high drug content (92.39%). In vitro release demonstrated sustained insulin release from nanoparticles (70.31% at 48 h) and films (66.15% at 48 h), while plain insulin solution released 99.01% within 6 h. Release followed first-order kinetics (r² = 0.9849), suggesting diffusion-controlled behaviour. Discussion Embedding insulin-loaded nanoparticles into HPMC/PVA films improved release sustainability and stability compared to conventional insulin solutions, indicating enhanced suitability for chronic wound applications. Conclusion The optimized nanoparticle-embedded film (F4) represents a promising platform for sustained topical insulin delivery, offering favourable physicochemical and mechanical attributes for diabetic wound management.