Development of Resveratrol/Curcumin Dual-Loaded Chitosan/Sericin Hydrogel Films for Wound Healing: A Comparison Of...

This study reports the formulation and comparative evaluation of resveratrol and curcumin dual-loaded chitosan-based wound-healing films prepared from shrimp-derived chitosan (Shrimp-CTS, ~ 80 kDa, degree of deacetylation of ~ 95%) and crab-derived chitosan (Crab-CTS, ~ 100 kDa, degree of deacetylation of ~ 85%). The film was prepared by crosslinking reaction of chitosan and glutaraldehyde, and the influence of chitosan origin on film structure, swelling, drug release, skin permeability, and in vivo wound healing was investigated. Morphological analyses revealed that shrimp-CTS-films possessed heterogeneous surfaces, whereas crab-CTS-films exhibited smoother surfaces. Swelling studies showed that shrimp-CTS-films displayed a burst swelling, reaching 75-85% swelling within 30-60 min, while the crab-CTS-films exhibited sustained swelling, progressively increasing to ~ 100% after 240 min. All drug release profiles followed biphasic kinetics (a burst release phase and a sustained phase) and fitted well to the Korsmeyer-Peppas model (R² > 0.90), suggesting anomalous transport governed by combined diffusion (mainly for shrimp-CTS) and polymer relaxation (mainly for crab-CTS). Ex vivo porcine skin studies confirmed superior permeability from crab-CTS-films, with cumulative permeation values approaching 85-100% at 300 min, compared to 50-80% for shrimp-CTS-films. Lastly, in vivo murine excisional wound models demonstrated that all films showed better healing performances than the commercial product (OctaCare®). Interestingly, the dual-loaded shrimp-CTS-films accelerated early wound closure to ~ 65-70% by day 3 and > 90% by day 7, whereas the dual-loaded crab-CTS-films promoted more consistent healing, achieving ~ 95-100% wound closure by days 14-21. In summary, these results demonstrate that chitosan sources affect the films' physicochemical properties, especially the phase-specific wound-healing outcomes.