Design, Optimization & Evaluation of Lovastatin-Loaded Polymeric Micelles for Enhanced Healing of Diabetic Wounds

Abstract

Introduction: Diabetic wounds are a major clinical challenge because of persistent inflammation, impaired angiogenesis, oxidative stress, and delayed extracellular matrix remodeling, all of which contribute to prolonged healing and increased risk of infection and amputation. Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, possesses pleiotropic properties such as anti-inflammatory activity, antioxidant effects, and upregulation of vascular endothelial growth factor (VEGF), making it a promising candidate for wound healing. However, its poor aqueous solubility and limited skin permeation restrict its topical therapeutic efficacy.

Aims & Objectives: This study aimed to develop and evaluate a lovastatin-loaded PEG–PCL polymeric micellar gel to enhance topical drug delivery and accelerate diabetic wound healing.

Materials & Methods: Lovastatin-loaded PEG–PCL polymeric micelles were prepared using the solvent evaporation method and incorporated into a carbopol gel. The formulation was characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug loading, in vitro drug release, and stability. Therapeutic efficacy was evaluated in streptozotocin-induced diabetic Wistar rats through wound contraction studies, epithelialization time, histopathological examination, and collagen deposition analysis.

Results: The optimized micellar formulation exhibited a particle size of 92.4 ± 6.3 nm, PDI < 0.2, and an entrapment efficiency of 88.6 ± 2.1%, with sustained drug release of approximately 85% over 24 h. In vivo studies demonstrated significantly enhanced wound contraction (95% by day 14), shorter epithelialization time, greater collagen deposition, and improved tissue regeneration compared with the conventional lovastatin gel (p < 0.001). Histopathological analysis confirmed increased angiogenesis, organized granulation tissue, and accelerated wound remodeling.

Conclusion: Lovastatin-loaded PEG–PCL polymeric micellar gel is a promising topical nanocarrier for improving diabetic wound healing by enhancing drug solubility, sustained release, angiogenesis, and tissue regeneration.