Pharmaceutical, clinical, and immunohistochemical studies of metformin hydrochloride topical hydrogel for wound healing application.

Wound healing could be categorized as a chronic disorder which needs a prompt and effective medication. Nowadays, vascular problems and wound-healing progression studies relay on the role of metformin; however, the exact mechanisms for its beneficial effects are still not completely understood. The aim of the present work was to study the potential of metformin hydrochloride, MET-HCL hydrogel in wound healing after topical administration. MET-HCL hydrogel was formulated using different hydrogel bases then characterised for its drug content and pH, homogeneity, viscosity, spreadability, and in vitro release. Furthermore, the wound-healing activity was evaluated in rats. Clinical study was also performed in patients showing lower limbs traumatic wounds and cutaneous ulcers. In addition, histopathology and immunohistochemical studies were also investigated. Results showed that MET-HCL hydrogels have a high drug content, and they are homogenous and spreadable with minimum sheer stress and showed null irritation. Furthermore, carbopol showed the optimum gel base for the highest MET-HCL release. Wound healing activity in rats showed a significant (p < 0.05) increase in the percentage wound contraction from the day-7 compared with plain hydrogel. Clinical study revealed a complete healing of traumatic wounds and cutaneous ulcers after 21 and 30 days, respectively. Moreover, histopathology investigation showed a complete restoration of connective tissue matrix and re-epithelization of the induced wound. In addition, immunohistochemistry showed a significant expression of transforming growth factor-β1 (TGF-β1). In conclusion, MET-HCL hydrogel is a promising formulation for topical treatment of wounds with effective and faster healing activity.