Topical delivery of high-drug-loading nanoparticle gels for psoriasis treatment.

Psoriasis is a chronic, immune-mediated skin disease characterised by epidermal hyperplasia and compromised barrier integrity, which significantly complicates effective drug delivery. Topical drug delivery (TDD) offers a promising, non-invasive, and patient-centric alternative therapy for its management. However, the efficacy of TDD is constrained by the markedly thickened stratum corneum in psoriatic lesion skin, which acts as a formidable barrier to effective drug penetration. In this work, we developed a high-drug-loading TDD system for the highly effective topical delivery of apremilast (APR), an FDA-approved oral treatment for psoriasis. Using a sequential nanoprecipitation method, lipid nanoparticles (LNPs) and polymer nanoparticles (PNPs) loaded with 40% APR, defined as the weight ratio of APR relative to the total nanoparticle formulation, were synthesized and embedded into Carbopol 940 gel for enhanced skin compatibility and topical application. Ex vivo studies revealed enhanced intradermal retention of LNPs Carbopol® 940 gel (LNPG) and greater subdermal accumulation of PNPs Carbopol® 940 gel (PNPG). In an imiquimod-induced psoriasis mouse model, treatment with both formulations resulted in marked clinical improvements, including reduced PASI scores, decreased epidermal thickness, and reduced spleen size. Furthermore, both LNPG and PNPG systems significantly downregulated psoriasis-associated cytokines (TNF-α, IL-1β, IL-6, CXCL8, and CCL20). These findings demonstrate the robust therapeutic potential of high-drug-loading NP gels and highlight their promise as a patient-friendly TDD platform for psoriasis and other dermatological conditions with a compromised barrier function.