Citric acid cross-linked pomegranate peel extract-loaded pH-responsive β-cyclodextrin/carboxymethyl tapioca starch hydrogel film for diabetic wound healing

• Published in: International journal of biological macromolecules 2024-08, Vol.274 (Pt 1), p.133366, Article 133366
• Main Authors: Savekar, Pranav L., Nadaf, Sameer J., Killedar, Suresh G., Kumbar, Vijay M., Hoskeri, Joy H., Bhagwat, Durgacharan A., Gurav, Shailendra S.
• Format: Article
• Language: English
• Subjects: Diabetes; Diabetic wound; Ellagic acid; Polysaccharides; Punica granatum
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133366

Pomegranate peel extract (PPE) hydrogel films filled with citric acid (CA) and β-cyclodextrin-carboxymethyl tapioca starch (CMS) were designed mainly to prevent wound infections and speed up the healing process. FTIR and NMR studies corroborated the carboxymethylation of neat tapioca starch (NS). CMS exhibited superior swelling behavior than NS. The amount of CA and β-CD controlled the physicochemical parameters of developed PPE/CA/β-CD/CMS films. Optimized film (OF) exhibited acceptable swellability, wound fluid absorptivity, water vapor transmission rate, water contact angle, and mechanical properties. Biodegradable, biocompatible, and antibacterial films exhibited pH dependence in the release of ellagic acid for up to 24 h. In mice model, PPE/CA/β-CD/CMS hydrogel film treatment showed promising wound healing effects, including increased collagen deposition, reduced inflammation, activation of the Wingless-related integration site (wnt) pathway leading to cell division, proliferation, and migration to the wound site. The expression of the WNT3A gene did not show any significant differences among all the studied groups. Developed PPE-loaded CA/β-CD/CMS film promoted wound healing by epithelialization, granulation tissue thickness, collagen deposition, and angiogenesis, hence could be recommended as a biodegradable and antibacterial hydrogel platform to improve the cell proliferation during the healing of diabetic wounds. •Carboxymethylation process of tapioca starch was optimized using factorial design.•Pomegranate peel extract-loaded film was prepared to promote diabetic wound healing.•Process parameters for hydrogel film formation were optimized by hexagonal design.•Biodegradable & biocompatible films showed pH dependent controlled drug release.•PPE/CA/β-CD/CMS hydrogel film facilitated wound healing in diabetic mice.