Development and evaluation of clobetasol propionate-loaded nanoliposomal hydrogel integrated with plant-derived microneedle-like microstructures for site-specific psoriasis therapy

Abstract

The hyperkeratotic stratum corneum is a principal barrier to the efficient topical treatment of psoriasis and limits drug penetration and therapeutic efficacy. In this regard, the aim of this study was to prepare a new topical delivery system containing clobetasol propionate (CP)-encapsulating nanoliposomes dispersed in Carbopol 940 hydrogel and various plant-derived microneedle-like structures for improved topical drug administration. The optimum formula (F2) had a vesicle size of 100 nm, a low polydispersity index (PDI; 0.152), a moderate zeta potential (−16 mV), and high encapsulation efficiencies of 98.8 ± 0.16% by the indirect method and 94.3 ± 0.49% by the direct method. Physicochemical analyses confirmed that CP was successfully incorporated, ensuring the preservation of structural integrity within the engineered nanoliposomal arrangement. The pH, viscosity, and spreadability of the optimized nanoliposomal hydrogel (F2Hb) were all within suitable ranges for the topical application of nanoliposomes. In vitro drug release studies indicated that the optimum nanoliposomal hydrogel formula (F2Hb) provided a sustained release profile; however, when plant-derived microneedle-like structures were incorporated into the nanoliposomal hydrogel (F2HbM), ex vivo skin deposition improved. In an imiquimod-induced mouse model of psoriasis, F2HbM significantly reduced erythema, scaling, and skin thickness and markedly decreased the levels of interleukin (IL)-17A and IL-23. These results indicated that the nanoliposomal hydrogel was an effective strategy for the topical delivery of CP, with sustained drug release and enhanced skin deposition via microneedle-like structures for the treatment of psoriasis.