Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

Cam M. E., ERTAŞ B., Alenezi H., YAVUZ A. N., Cesur S., Ozcan G. S., ...More

MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, vol.119, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 119
  • Publication Date: 2021
  • Doi Number: 10.1016/j.msec.2020.111586
  • Journal Name: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, Chemical Abstracts Core, Communication Abstracts, Compendex, EMBASE, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Keywords: Diabetic wound healing, Pioglitazone, Metformin, Glibenclamide, Drug delivery, Pressurized gyration, Electrospinning, GELATIN, METFORMIN, CHITOSAN, HYPERGLYCEMIA, PIOGLITAZONE, FABRICATION, RECEPTOR, DELIVERY, PPAR, GLIBENCLAMIDE
  • Gazi University Affiliated: Yes

Abstract

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.