Diabetic Foot Ulcers Healing Promoted by Novel Glibenclamide-loaded Micelle Wound Dressing

Abstract

Diabetic foot ulcers (DFU) are chronic wounds, which do not respond to traditional wound treatments. In this work, wound dressings of glibenclamide (GB) incorporated into a  novel mixed matrix were fabricated in the aim of accelerating the healing process of diabetic wounds. GB was loaded into different weight ratios of Soluplus® (SP) and polyvinylpyrrolidone (PVP). The developed dressings were characterized İn vitro and in vivo, for their ability to promote diabetic wound healing. The particle size was between (1.4-2) µm. The morphology abided by the SP/PVP ratio in the formulated microparticles. Cup/bowl shape, semispherical with corrugated surface, apple shape with smooth surface, concave/star shape, and Irregular corrugated morphology were denoted for GB-SP/PVP1-0, GB-SP/PVP1-1, GB-SP/PVP0-1, GB-SP/PVP1-2, and GB-SP/PVP2-1 formulations, respectively. Glibenclamide was in amorphous form and hydrogen-bonded with the matrix polymers. The GB-SP/PVP0-1 wound dressings showed a burst drug release in about 1 hour due to the hydrophilic nature of PVP. The other GB-SP/PVP formulated polymeric micelles were of sustained release, where GB-SP/PVP2-1 extended the drug release for 48 hours. The MTT assay showed that all GB-SP/PVP dressings have good cytocompatibility, and in consequence, they can be used in further investigations on biomedical applications. In vivo tests on a rat model of a full-thickness wound showed rapid closure, indicating the success of the wound dressings in decreasing inflammation and promoting wound healing without scar formation. Therefore, topical administration of GB-SP/PVP1-0 and GB-SP/PVP2-1 wound dressings has a high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic adverse effects.