Preparation and in vitro-in vivo evaluation of new gallic acid loaded poloxamer/sodium alginate based thermoresponsive and bioadhesive in situ gels for wound treatment

Abstract

In this study, Poloxamer based in situ gels were developed and characterized to formulate a successful dressing and to give a new impulse to wound treatment. These gels were formulated with 2 % Gallic acid (GA), using Poloxamer 407 (P407), Poloxamer 188 (P188), and sodium alginate with cold method in various concentrations to develop thermoresponsive and bioadhesive gels utilizing the healing effect of GA. The in situ gels with the suitable gelation temperature were selected for further studies. They underwent a thorough evaluation, including clarity, gelling capacity, pH, drug content, viscosity, spreadability, mechanical properties, bioadhesion, and in vitro release studies. Notably, the F8 (20 % P407, 5 % P188, 1 % sodium alginate) demonstrated the highest adhesiveness (37.22 +/- 8.65 g s) value in mechanical examination, which is one of the most important factors of bioadhesive formulations, corresponding required strength as well as preventing leakage at the same time. It was also supported by ex vivo bioadhesion (0.23 +/- 0.29 N) results among the formulations. The in vitro release studies revealed that each formulation was capable of releasing GA up to 100 % within 4 h. Following these results, further ex vivo permeation, penetration studies, and biological assays were examined. F8 stood out, showing superior performance in wound healing, nitric oxide (NO) measurement, analgesic activity, and IL-6 release, all while displaying no cytotoxic effects. In vivo experiments further confirmed the efficacy of GA loaded in situ gels, showing the lowest inflammatory cell concentration, the thickest granulation tissue, the highest level of epidermal regeneration, and the densest collagen and new vessel formation compared to other groups. These findings suggest that new in situ gels hold great promise for safe and effective wound treatment.