Multi-component clobetasol-loaded monolithic lipid-polymer hybrid nanoparticles ameliorate imiquimod-induced psoriasis-like skin inflammation in Swiss albino mice

Abstract

Lipid-polymer hybrid nanoparticles (LPNs) exhibit several advantages over polymeric and non-polymeric systems in terms of improved drug loading, controlled release, stability, and cellular uptake. Herein we report a scalable and stable monolithic lipid-polymer hybrid nanoparticles (LPNs) consisting of a combination of lipids (solid and liquid) and an amphiphilic copolymer, mPEG-PLA. Clobetasol propionate, a topical corticosteroid, was encapsulated in the hydrophobic core of these LPNs that showed spherical shaped particles with a z-average size of 94.8 nm (PDI = 0.213) and encapsulation efficiency of 84.3%. These clobetasol loaded LPNs (CP/LPNs) were formulated into a topical hydrogel using carbopol 974P. CP/LPNs gel showed a sustained in vitro clobetasol release for 7 days with no burst release and 6 month stability at 2-8°C and room temperature. Further, CP/LPNs showed an improved cellular uptake with significant growth inhibition of HaCaT cells. In ex vivo studies, these LPNs penetrated into the viable epidermis and dermis region of the psoriatic skin with undetectable quantities leaching to the reservoir. Further, the topical application of CP/LPNs gel on Swiss albino mice with psoriasis-like inflammation showed negligible leaching of clobetasol into the systemic circulation. Efficacy assessment showed significantly improved PASI score, reduced skin damage and proliferation after treatment with CP/LPNs gel as compared to marketed product (Clobetamos™). Collectively, the enhanced cellular uptake, high skin penetration with increased skin retention, and improved efficacy demonstrate the potential of these LPNs for future clinical application.