Development of solid lipid nanoparticles to deliver triptolide for topical treatment of psoriasis

Abstract

Psoriasis is a chronic inflammatory disease of the skin and joints, immune-mediated, genetically based, with great polymorphism of clinical expression, affecting both men and women equally. Triptolide (TP) has been an effective drug in the treatment of psoriasis, mediating various inflammatory pathways, thus being an important immunosuppressant. However, due to multiple organ toxicity associated with its systemic use and irritation caused by topical use in free form, TP is not widely used therapeutically. Therefore, it has been investigated alternative methods for topical administration of TP in order to decrease the toxic effects, lower the dose required to elicit a therapeutic effect, increase the penetration of the drug into the skin and increase drug residence time at the site of action. Among the strategies that have been investigated, it can be included the use of nanostructured systems such as solid lipid nanoparticles (SLN), which are the focus of this project. Thus, this project aims to develop SLN incorporated with TP, in order to obtain a system for topical application to properly release the TP into the skin without causing irritation and/or toxicity, as a future proposal for topical treatment of psoriasis. The nanoparticles will be obtained by both hot homogenization and high pressure homogenization methods, being further characterized in respect to diameter and zeta potential, by dynamic light scattering and electrophoresis mobilididade. TP encapsulation efficiency and its in vitro release and skin permeation, using synthetic membrane and skin of pig's ear, will also be evaluated.