Trinitroglycerin-loaded chitosan nanogels accelerate angiogenesis in wound healing process

Int J Biol Macromol. 2024 Oct;278(Pt 3):134937. doi: 10.1016/j.ijbiomac.2024.134937. Epub 2024 Aug 22.

Abstract

Trinitroglycerin (TNG) with remarkable angiogenic, antibacterial, and antioxidative activity is a promising candidate to govern wound healing capacity. However, its clinical administration is limited due to associated complications and NO short half-life. In the current study, TNG-loaded chitosan nanogels (TNG-Ngs) were examined in-vitro and in-vivo to gain insight into their clinical application. We prepared TNG-Ngs and characterized their physiochemical properties. The potential of TNG-Ngs was assessed using biocompatibility, scratch assay, and a full-thickness skin wounds model, followed by histopathological and immunohistochemistry examinations. TNG-Ngs particle size 96 ± 18 and definite size distribution histogram. The loading capacity (LC) and encapsulation efficiency (EE) of prepared TNG-Ngs were 70.2 % and 2.1 %, respectively. The TNG-Ngs samples showed enhanced migration of HUVECs with no apparent cytotoxicity. The topical use of TNG-Ngs200 on the wounds revealed a complete wound closure ratio, skin component formation, less scar width, remarkable granulation tissue, promoted collagen deposition, and enhanced the relative mean density of α-SMA and CD31. TNG-Ngs accelerated wound healing by promoting collagen deposition and angiogenic activity, as well as reducing inflammation. The findings indicated that TNG-Ngs is expected to be well vascularized in the wound area and to be more effective in topical therapy.

Keywords: Angiogenesis; Chitosan; Nanogels; Natural polymer; Trinitroglycerin; Wound healing.

MeSH terms

  • Angiogenesis
  • Animals
  • Cell Movement / drug effects
  • Chitosan* / chemistry
  • Chitosan* / pharmacology
  • Human Umbilical Vein Endothelial Cells* / drug effects
  • Humans
  • Mice
  • Nanogels* / chemistry
  • Neovascularization, Physiologic* / drug effects
  • Particle Size
  • Rats
  • Skin / drug effects
  • Skin / injuries
  • Skin / metabolism
  • Wound Healing* / drug effects

Substances

  • Chitosan
  • Nanogels