Rapamycin loaded lipid-polymer hybrid nanoparticles in a topical hydrogel for the treatment of psoriasis.

Lipid-Polymer Hybrid Nanoparticles (LPHNs) offer significant advantages in drug delivery systems due to their enhanced drug loading, controlled release, and stability. This study focuses on developing and evaluating Rapamycin-loaded LPHNs (RAPA/LPHNs) for effective psoriasis treatment. RAPA/LPHNs were formulated at 0.2% and 0.5% w/w drug loading using hot homogenisation, showing particle sizes of 140.5 nm and 171.4 nm, with polydispersity indices of 0.222 and 0.206, and encapsulation efficiencies of 86 % and 78 %, respectively. The nanoparticles were subsequently incorporated into a topical hydrogel (RAPA/LPHNs gel) formulated with Carbopol 974. The RAPA/LPHNs and RAPA/LPHNs gel exhibited sustained in vitro drug release over 5 days, while the gel maintained good stability with a viscosity of 8,562 cP. In vivo studies on psoriasis-induced Swiss Albino mice demonstrated a significant therapeutic effect of the prepared gel, with a Psoriasis Area and Severity Index (PASI) score of 2.0 for the RAPA/LPHNs gel (0.5%w/w), compared to 3.8 for the marketed formulation (Tenovate™) and 8.4 for the positive control. Histopathological study showed restoration of normal epidermal structure with reduced hyperkeratosis and inflammatory infiltration in RAPA/LPHNs gel. Immunohistochemistry analysis further confirmed downregulation of psoriatic inflammatory markers (TNF-α and IL-17). This study underscores the potential of RAPA/LPHNs in enhancing psoriasis therapy through improved drug delivery, sustained release, and reduced systemic toxicity.