Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study
The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also
exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into
chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL
composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing
effect. The combination therapies significantly accelerated diabetic wound healing in type-1
diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better
regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory
cell infiltration and edema. The formation of the hair follicles started in 14 days only in the
combination therapy and lower proinflammatory cytokine levels were observed compared to single
drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity
of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and
suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the
proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded
chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability,
fewer systemic side effects, and reduced frequency of dosage and amount of drug