Topical co-delivery of methotrexate and etanercept using lipid nanoparticles: A targeted approach for psoriasis management

Abstract

Methotrexate is indicated in psoriasis systemic therapy and its topical administration may be an option to overcome several side effects. A targeted delivery may be achieved through etanercept. Thus, a combination targeted therapy using methotrexate and etanercept could bring new perspectives for psoriasis patients. This work intended to develop and characterize co-delivery of methotrexate and etanercept using lipid nanoparticles, mediated by a carbopol hydrogel and to evaluate their potential for delivering the drug into the skin with reduced transdermal permeation. The nanoparticles were physico-chemically characterized. In vitro methotrexate release from solid lipid nanoparticles revealed a sustained release for 8h. The solid lipid nanoparticles were non-toxic towards human keratinocytes and fibroblasts. Permeation studies using pig ear as model revealed enhanced skin deposition of the applied methotrexate when incorporated within solid lipid nanoparticles in relation to free drug. Therapeutic amounts of methotrexate were delivered to psoriatic human skin after application of solid lipid nanoparticles, with reduced transdermal permeation.

Keywords: Carbopol hydrogel; Etanercept; HaCaT keratinocytes; Human skin permeation; Methotrexate; Psoriatic skin; Solid lipid nanoparticles.