Alpha tocopherol loaded chitosan oleate nanoemulsions for wound healing. Evaluation on cell lines and ex vivo human biopsies, and stabilization in spray dried Trojan microparticles

Eur J Pharm Biopharm. 2018 Feb:123:31-41. doi: 10.1016/j.ejpb.2017.11.008. Epub 2017 Nov 15.

Abstract

An amphiphilic chitosan salt, chitosan oleate (CS-OA), was previously proposed for the physical stabilization of lemongrass antimicrobial nanoemulsions (NE) through a mild spontaneous emulsification process. As both chitosan and oleic acid are described in the literature for their positive effects in wound healing, in the present study CS-OA has been proposed to encapsulate alpha tocopherol (αTph) in NEs aimed to skin wounds. A NE formulation was developed showing about 220 nm dimensions, 36% drug loading, and αTph concentration up to 1 mg/ml. Both CS-OA and αTph NE stimulated cell proliferation on keratinocytes and fibroblast cell cultures, and in ex vivo skin biopsies, suggesting the suitability of CS-OA and of the antioxidant agent for topical application in wound healing. αTph stability was further improved with respect of encapsulation, by spray drying the NE into a powder (up to about 90% αTph residual after 3 months). The spray drying process was optimized, to improve powder yield and αTph recovery, by a design of experiments approach. The powder obtained was easily re-suspended to deliver the NE and resulted able to completely release αTph.

Keywords: Alpha tocopherol; Chitosan; Nanoemulsion; Oleic acid; Wound healing.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Antioxidants / metabolism
  • Biopsy
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical / methods
  • Chitosan / chemistry*
  • Drug Delivery Systems / methods
  • Emulsions / administration & dosage*
  • Emulsions / chemistry
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Oleic Acid / chemistry*
  • Particle Size
  • Powders / administration & dosage
  • Powders / chemistry
  • Wound Healing / drug effects*
  • alpha-Tocopherol / administration & dosage*
  • alpha-Tocopherol / chemistry

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Emulsions
  • Powders
  • Oleic Acid
  • Chitosan
  • alpha-Tocopherol