Combinatorial treatment of mupirocin nanomicelle in insulin-based gel for wound healing in diabetic rats

Abstract

Abstract Background: Diabetic wounds remain an important clinical challenge over the past few decades. Nanodrug delivery systems play a crucial role in the treatment of chronic infections and wound healing. Objectives: To evaluate the wound healing potential of newly synthesized and characterized mupirocin (MP) nanomicelle (NM) in insulin (I)-based gel (MP-NM-I), utilizing alloxan-induced diabetic rat model. Materials and Methods: MP-NM-I was prepared by solvent evaporation technique, 96 male rats were assigned randomly into eight groups (n = 12): one group is healthy, and the remaining seven groups were diabetic and wounded receiving treatments of gel base, tween 80, I, MP, MP-I, MP-NM, and MP-NM-I, respectively. Rats were sacrificed after 7 and 14 days of wounding. Blood samples were collected for glucose and insulin concentration measurement. Skin biopsies were examined by histological and immunohistochemical analyses. Results: Diabetes was confirmed after a significant increase in blood glucose and a decrease in serum insulin concentrations (P ≤ 0.001). MP-NM– and MP-NM-I–treated groups presented a rapid wound closure (100 ± 0, P ≤ 0.001), and the bacterial growth in these samples was relatively low (P ≤ 0.001). Histological examination established a significant decrease in inflammatory cells (P ≤ 0.001) with a significant elevation in tissue re-epithelialization, fibroblasts, angiogenesis, and collagen fibers (P ≤ 0.001). Immunohistochemical investigation presented a significant decrease in tumor necrosis factor-α, increase in vascular endothelial growth factors, and interleukin-10 scores (P ≤ 0.001). Conclusion: The developed formula of MP-NM with or without insulin is more effective than MP alone for diabetic wound healing in rats, because it accelerated wound closure. Accordingly, the formula might serve as an innovative tool for diabetic wound healing.