Effects of topical methotrexate loaded gold nanoparticle in cutaneous inflammatory mouse model

Nanomedicine. 2019 Apr:17:276-286. doi: 10.1016/j.nano.2019.01.006. Epub 2019 Jan 30.

Abstract

Gold nanoparticles functionalized with 3-mercapto-1-propansulfonate (AuNPs-3MPS) have been prepared and loaded with Methotrexate (MTX), an immunosuppressive agent used in the systemic treatment of moderate-severe inflammatory diseases. The effects of the AuNPs-3MPS@MTX topically administered in vitro on skin model and in vivo on imiquimod-induced psoriasis-like mice model, have been studied. Clinical response, epidermal thickness, cell proliferation rate and inflammation were tested. AuNPs-3MPS@MTX treated mice showed a decreasing of scaling and erythema score, reduction of epidermal thickness, parakeratosis and hyperkeratosis, compared to AuNPs-3MPS treated mice. Immunohistochemistry analysis staining displayed that Ki67, K6 CD3 and CD8 stainings were reduced in AuNPs-3MPS@MTX treated mice. Blood evaluation showed no differences in blood count and in ALT and AST levels before and after AuNPs-3MPS or AuNPs-3MPS@MTX treatment. Topical AuNPs-3MPS@MTX treatment is able to induce a reduction of keratinocytes hyperproliferation, epidermal thickness and also inflammatory infiltrate in vivo on imiquimod-induced psoriasis like mice model.

Keywords: Functionalized gold nanoparticle; Methotrexate transepidermal delivery; Percutaneous delivery; Topical psoriasis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Gold / chemistry*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / therapeutic use
  • Metal Nanoparticles / chemistry
  • Methotrexate / administration & dosage*
  • Methotrexate / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Psoriasis / drug therapy*
  • Sulfhydryl Compounds / chemistry*

Substances

  • 3-mercapto-1-propanesulfonate
  • Drug Carriers
  • Immunosuppressive Agents
  • Sulfhydryl Compounds
  • Gold
  • Methotrexate