Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch

Eur J Pharm Biopharm. 2024 Aug:201:114347. doi: 10.1016/j.ejpb.2024.114347. Epub 2024 May 31.

Abstract

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Keywords: Ionizing radiation; Microneedles; PEGylated superoxide dismutase; Radiation dermatitis; Transdermal delivery.

MeSH terms

  • Administration, Cutaneous*
  • Animals
  • Male
  • Mice
  • Needles*
  • Polyethylene Glycols* / chemistry
  • Radiation-Protective Agents / administration & dosage
  • Radiation-Protective Agents / pharmacokinetics
  • Radiation-Protective Agents / pharmacology
  • Radiodermatitis* / prevention & control
  • Skin Absorption* / drug effects
  • Skin* / drug effects
  • Skin* / metabolism
  • Skin* / radiation effects
  • Superoxide Dismutase* / administration & dosage
  • Superoxide Dismutase* / metabolism
  • Transdermal Patch*

Substances

  • Polyethylene Glycols
  • Superoxide Dismutase
  • Radiation-Protective Agents