pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharide promotes diabetic wound healing by enhancing angiogenesis and antibacterial activity

Drug Deliv Transl Res. 2019 Feb;9(1):227-239. doi: 10.1007/s13346-018-00609-8.

Abstract

Diabetic wounds as chronic wounds represent a severe, persistent complication of diabetes and, in the most extreme cases, can lead to amputation. Two critical and unfavorable factors affecting diabetic wound healing are sustained bacterial-induced chronic inflammation and disrupted vascularization. In this paper, we presented a novel, pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharides, and explored its potential for accelerating diabetic wound healing. A thorough investigation indicated that the drug- and nanoparticle-loaded hydrogel demonstrated strong bactericidal behavior mediated by protamine nanoparticles and reduced bacterial-induced chronic inflammation at the wound site. Furthermore, it accelerated the wound-healing process by promoting angiogenesis in skin wounds with the hyaluronan oligosaccharide-mediated enhanced expression of vascular endothelial growth factor.

Keywords: Bacterial; Calcium alginate hydrogel; Diabetes; Inflammation; Nanoparticles; Protamine.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Anti-Bacterial Agents
  • Diabetes Mellitus, Experimental / complications*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hydrogels / chemistry
  • Hydrogen-Ion Concentration
  • Nanoparticles / chemistry
  • Neovascularization, Physiologic / drug effects*
  • Protamines / administration & dosage*
  • Protamines / chemistry
  • Protamines / pharmacology
  • Rats
  • Streptozocin
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*

Substances

  • Alginates
  • Anti-Bacterial Agents
  • Hydrogels
  • Protamines
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Streptozocin
  • Hyaluronic Acid