A one-stop integrated natural antimicrobial microneedles with anti-inflammatory, pro-angiogenic and long-term moisturizing properties to accelerate diabetic wound healing

Eur J Pharm Biopharm. 2024 Oct:203:114448. doi: 10.1016/j.ejpb.2024.114448. Epub 2024 Aug 10.

Abstract

Diabetic ulcers present a formidable obstacle in diabetes management, typically leading to high mortality and amputation rates. To overcome traditional monotherapy drawbacks, We developed a novel microneedle strategy for combined antimicrobial action: ingeniously integrating quercetin with Platelet-derived Growth Factor-BB(PDGF-BB) and Sucrose Octasulfate(SOS) into the microneedle system(QPS MN). This method allows to penetrate through biofilms, administering quercetin nanocrystals and PDGF-BB deep into the tissue to combat microbial infection, mitigate inflammation, and promote angiogenesis. The accompanying backing material contains SOS, which absorbs wound exudate and forms a dressing that provides a moist environment for wound healing In an in vitro wound-scratch assay demonstrated that co-cultivating Human Umbilical Vein Endothelial Cells(HUVEC) with QPS MN for 48 h (90.3 ± 2.51 %) significantly enhanced cell migration compared to the control group (20.2 ± 1.41 %). Moreover, treatment of streptozotocin-induced diabetic wounds in rats with QPS MN for 14 days resulted in a wound healing rate of 96.56 ± 3.44 %, far surpassing the healing rate of only 40.34 ± 7.26 % observed in the untreated control group. Furthermore, the QPS MN treated wounds exhibited a notable increase in skin appendages and neovascularisation, indicating promising potential for achieving complete wound healing. These results suggest that QPS MN may offer substantial therapeutic benefits for addressing diabetic wounds.

Keywords: Diabetic wounds; Dissolving microneedles; PDGF-BB; Quercetin nanocrystals; Sucrose octasulfate.

MeSH terms

  • Angiogenesis Inducing Agents / administration & dosage
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / pharmacology
  • Anti-Inflammatory Agents* / administration & dosage
  • Anti-Inflammatory Agents* / pharmacology
  • Becaplermin / administration & dosage
  • Becaplermin / pharmacology
  • Cell Movement / drug effects
  • Diabetes Mellitus, Experimental* / drug therapy
  • Human Umbilical Vein Endothelial Cells* / drug effects
  • Humans
  • Male
  • Nanoparticles / chemistry
  • Needles*
  • Neovascularization, Physiologic / drug effects
  • Quercetin / administration & dosage
  • Quercetin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing* / drug effects

Substances

  • Anti-Inflammatory Agents
  • Becaplermin
  • Quercetin
  • Anti-Infective Agents
  • Angiogenesis Inducing Agents