Synergistic Nano-Therapeutic Approach for Psoriasis: Targeting TNF-α and IL-17 Pathways via Transdermal Delivery

Psoriasis, affecting 2-3% of the global population and 20 million individuals in Europe, poses significant challenges in treatment efficacy and patient adherence to current therapies. Addressing these challenges, this project proposes an innovative therapeutic strategy by integrating Etanercept (ETR), a TNF- inhibitor, with small interfering RNA (siRNA) targeting IL-17A, facilitated through a novel transdermal delivery method. The project aims to develop and optimize hybrid lipid-polymer nanoparticles (LPNs) for co-delivering ETR and siRNA. These LPNs will be incorporated into microneedles (MNs) composed of biocompatible polymers, pectin, and polycaprolactone (PCL). This dual delivery approach leverages LPNs' controlled release properties and MNs' enhanced skin permeability to target multiple pathogenic pathways involved in psoriasis synergistically. Specific objectives include optimizing LPN formulation, evaluating efficacy in vitro, characterizing the MN system for skin penetration, and assessing performance in ex vivo psoriasis models, guided by ethical principles (3Rs: Replacement, Reduction, and Refinement). Expected outcomes encompass improved treatment efficacy, reduced adverse effects, and enhanced patient adherence, thereby advancing psoriasis management. Furthermore, this project seeks to catalyze interdisciplinary collaborations and propel the development of novel therapeutic strategies, contributing to scientific innovation and healthcare advancement.