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Skin-permeable gold nanoparticles with modifications azelamide monoethanolamine ameliorate inflammatory skin diseases
He Zhao1,2,3, Han Zhao1,2,3, Yan Tang1,2,3
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
Background:
Traditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases.
Methods:
Here, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs.
Results:
We found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9.
Conclusion:
Au-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.
