Comprehensive developmental investigation on simvastatin enriched bioactive film forming spray using the quality by design paradigm: a prospective strategy for improved wound healing

J Drug Target. 2024 Nov;32(9):1139-1153. doi: 10.1080/1061186X.2024.2382405. Epub 2024 Jul 29.

Abstract

The use of topical antimicrobials in wound healing presents challenges like risk of drug resistance and toxicity to local tissue. Simvastatin (SIM), a lipid-lowering agent which reduces the risk of cardiovascular events, is repurposed for its pleiotropic effect in wound healing. A bioactive bioadhesive polymer-based film forming spray (FFS) formulation of SIM was designed using chitosan, collagen, hyaluronic acid and optimised by employing the DoE approach. Optimised formulation demonstrated moderate viscosity (12.5 ± 0.3 cP), rapid film formation (231 ± 5.6 s), flexibility, tensile strength and sustained drug release (T80 - time for 80% drug release - 9.05 ± 0.7 h). Scanning electron microscopy (SEM) verified uniformly dispersed drug within the composite polymer matrix. SIM FFS demonstrated antimicrobial activity against gram positive and gram negative bacteria. In vivo excision wound model studies in mice affirmed the beneficent role of bioactive polymers and the efficacy of SIM FFS in wound contraction and closure, tissue remodelling and re-epithelization in comparison to standard antimicrobial preparation. Cytokines TNF- alpha, IL-6 were downregulated and IL-10 was upregulated. Biochemical markers; hydroxyproline, hexosamine and histopathology were consistent with wound contraction observed. This is an exploratory effort in repurposing SIM for wound healing in a novel dosage form, underscoring its potential as an alternative to conventional topical antimicrobials.

Keywords: Film forming spray; chitosan; collagen; hyaluronic acid; simvastatin; wound healing.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Chitosan / chemistry
  • Collagen
  • Delayed-Action Preparations
  • Drug Liberation
  • Hyaluronic Acid* / chemistry
  • Male
  • Mice
  • Simvastatin* / administration & dosage
  • Simvastatin* / chemistry
  • Simvastatin* / pharmacology
  • Wound Healing* / drug effects

Substances

  • Simvastatin
  • Hyaluronic Acid
  • Chitosan
  • Collagen
  • Anti-Bacterial Agents
  • Delayed-Action Preparations