Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery

Acta Pharmacol Sin. 2020 Jan;41(1):119-128. doi: 10.1038/s41401-019-0288-7. Epub 2019 Sep 18.

Abstract

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

Keywords: 20 (S)-protopanaxadiol; diabetic ulcer; nanostructured lipid carrier; ordered recovery; scarless wound healing; silicone elastomer.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Diabetic Foot / drug therapy*
  • Diabetic Foot / pathology
  • Drug Carriers / chemistry
  • Drug Liberation
  • Gels / administration & dosage
  • Gels / chemistry
  • Humans
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Lipids / chemistry
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Nanostructures / chemistry
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Particle Size
  • RAW 264.7 Cells
  • Sapogenins / administration & dosage
  • Sapogenins / chemistry
  • Sapogenins / pharmacology*
  • Silicone Elastomers / administration & dosage
  • Silicone Elastomers / chemistry*
  • Surface Properties
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Carriers
  • Gels
  • Lipids
  • Lipopolysaccharides
  • Sapogenins
  • Silicone Elastomers
  • Nitric Oxide
  • protopanaxadiol