Development and Optimization of a Lupeol-Loaded Bilosomal Gel for Enhanced Topical Therapy of Imiquimod-Induced Psoriasis

Lupeol, a naturally occurring pentacyclic triterpenoid, exhibits potent anti-inflammatory and antioxidant activities, making it a promising candidate for psoriasis treatment. However, its poor aqueous solubility and limited skin permeation restrict its therapeutic application. This study aimed to develop and optimize a lupeol-loaded bilosomal gel to enhance topical delivery and improve anti-psoriatic efficacy. Lupeol-loaded bilosomes were prepared using the thin-film hydration method and optimized through a Box–Behnken experimental design. The optimized formulation was characterized for vesicle size, entrapment efficiency, drug release, and physicochemical properties before incorporation into a Carbopol® 934P gel. The bilosomal gel was further evaluated through in vitro drug release, ex vivo skin permeation, and in vivo efficacy in an imiquimod-induced psoriasis-like mice model. The optimized bilosomes exhibited nanoscale vesicles, high drug entrapment, and sustained drug release. Incorporation into the gel produced a formulation with suitable physicochemical characteristics and significantly enhanced skin permeation compared with a conventional gel. In vivo, the bilosomal gel markedly reduced Psoriasis Area and Severity Index (PASI) scores, spleen index, and TNF-α levels while restoring normal skin histology. These findings demonstrate that bilosomal encapsulation substantially improves the topical delivery and therapeutic efficacy of lupeol, highlighting the developed bilosomal gel as a promising nanocarrier-based strategy for the topical management of psoriasis.