Topical Delivery of Vorinostat-Loaded Lyotropic Liquid CrystallineNanoparticles Gel for the Treatment of Psoriasis

INTRODUCTION: Lyotropic liquid crystalline nanoparticles (LLCs) are promising nanocarriers for topical drug delivery due to their ability to enhance bioavailability and reduce systemic side effects. This study aimed to develop and evaluate a vorinostat-loaded LLCs gel for the treatment of psoriasis, to improve skin drug retention, therapeutic efficacy, and patient compliance. METHODS: Vorinostat-loaded LLCs were prepared using glycerol monooleate as the lipid phase and Poloxamer 407 as a stabilizer. The nanoparticles were characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The LLCs were incorporated into a Carbopolbased gel and evaluated for in vitro drug release, skin permeation, and retention. In vivo efficacy was assessed in an imiquimod-induced psoriasis mouse model using PASI scoring, histopathology, and Ki-67 immunohistochemistry. RESULTS: The LLCs showed a particle size of 236.6 ± 7.05 nm, PDI of 0.27 ± 0.04, zeta potential of - 17.42 ± 0.28 mV, and entrapment efficiency of 81.65 ± 1.12%. Incorporation into gel enhanced skin drug retention by fourfold compared to plain vorinostat gel. The gel demonstrated sustained drug release up to 72 h without a burst effect. In vivo, vorinostat LLCs gel (0.05%) significantly reduced PASI scores, normalized histological features, and decreased Ki-67 expression compared to plain gel and marketed formulation. DISCUSSION: The enhanced therapeutic efficacy is due to the skin-lipid interactions of LLCs and their inherent hydrating properties, which together promote improved skin penetration, prolonged drug retention within the skin layers, and restoration of the skin barrier. Reduced systemic absorption further minimizes potential adverse effects, while the topical route ensures targeted delivery directly to psoriatic lesions. CONCLUSION: Vorinostat-loaded LLCs gel offers a stable, sustained-release, and skin-retentive formulation that significantly improves psoriasis treatment outcomes.