Improving the efficacy of tazarotene in psoriasis via bilosomal gel delivery: in vitro characterization, ex vivo evaluation, and preclinical assessment in an imiquimod induced psoriasis in a rat model.

Abstract

Bilosomes (BLs) loaded with tazarotene (TZ) were developed to enhance dermal delivery for psoriasis management. Vesicles were prepared using the thin-film hydration technique and optimized using 32 full factorial design to maximize entrapment efficiency (EE%) and zeta potential (ZP) while minimizing particle size (PS). The optimized bilosomal formulation (Opt-BLs), was evaluated for morphology and elasticity, then incorporated into a 1% Carbopol gel (Opt-BLs gel), which was further characterized for rheological behavior, storage stability (4 to 8°C, 3 months), and ex vivo skin permeation and deposition. The anti-psoriatic activity of the gel was subsequently assessed using an imiquimod induced rat model. The Opt-BLs exhibited an EE% of 90.27 ± 0.93%, PS of 451.39 ± 26.05 nm, ZP of -52.11 ± 2.76 mV, and PDI of 0.48 ± 0.06, with high elasticity. The Opt-BLs gel demonstrated pseudoplastic rheological behavior, supporting ease of application and prolonged residence at the application site, while maintaining physicochemical stability. Ex vivo studies showed enhanced skin deposition (389.12 ± 14.08 µg/cm2), indicating localized drug retention within the skin layers. In vivo, the Opt-BLs gel demonstrated greater therapeutic improvement compared with the commercial product (Acnitaz®), as reflected by the lowest increase in ear thickness (5.5 ± 0.72 x10-2 mm), reduced spleen index (0.0087 ± 0.001), and a PASI score of 3. Histopathological evaluation confirmed the restoration of skin architecture with minimal inflammatory infiltration. These findings indicate that the Opt-BLs gel represents a stable and deformable vesicular system that enhances dermal delivery and therapeutic performance of tazarotene in psoriasis.