DESIGN AND OPTIMIZATION OF TRANSETHOSOMAL GEL LOADED WITH HERBAL EXTRACTS FOR ACCELERATED DIABETIC WOUND HEALING

Abstract

Diabetic wounds represent a major clinical challenge due to impaired angiogenesis, delayed re-epithelialization, and chronic inflammation. The present study aimed to design and optimize a transethosomal gel incorporating standardized herbal extracts of Centella asiatica, Aloe vera, and Azadirachta indica for accelerated diabetic wound healing. Transethosomes were developed using phosphatidylcholine, ethanol, and Tween 80 as permeation enhancers and formulated by thin-film hydration. A Box–Behnken design (BBD) was employed to optimize the effects of lipid concentration, ethanol content, and surfactant ratio on vesicle size, entrapment efficiency, and zeta potential. Optimized transethosomes (mean size 162.4 ± 4.7 nm, PDI 0.21, zeta potential −38.6 mV, and 82.5% entrapment efficiency) were incorporated into a Carbopol 940-based hydrogel. The transethosomal gel demonstrated superior physicochemical stability, sustained drug release over 24 h (87.3% cumulative release), and enhanced skin permeation compared to conventional gel. In vitro cell migration (scratch assay) using NIH 3T3 fibroblasts indicated 92.4% wound closure within 24 h. In streptozotocin-induced diabetic rats, topical application of the optimized gel significantly improved wound contraction (96.8% by day 14), collagen deposition, and histopathological regeneration relative to control and marketed formulations. The synergistic antioxidant, antimicrobial, and angiogenic activities of the herbal extracts, combined with the deformable vesicular nature of transethosomes, contributed to enhanced therapeutic efficacy. The developed transethosomal herbal gel presents a promising, biocompatible, and cost-effective platform for the treatment of chronic diabetic wounds.