Development and Optimization of a Nanophytosomes‐Based Thermogel as a Topical Anti‐Psoriatic for Increased Solubility and Bioavailability

ABSTRACT Herbal extracts often demonstrate promising in vitro activity but limited in vivo efficacy due to poor solubility, permeability, and stability. Phytosomal delivery systems offer a strategy to increase the transdermal delivery and bioavailability. This study aimed to develop and optimize a Leucas aspera phytosomal thermogel for improved topical treatment of psoriasis. Phytosomes were‐prepared from phospholipid complexes and optimized via a Box–Behnken design. The optimized formulation was evaluated for vesicle size, zeta potential, entrapment efficiency (EE), in vitro drug release, and skin deposition. Anti‐psoriatic efficacy was assessed in an imiquimod induced psoriasis mouse model through PASI scoring, ear thickness measurement, organ index analysis, transepidermal water loss and hydration studies, and histopathology. The optimized PHY gel exhibited a particle size of 92.23 ± 9.1 nm, zeta potential of −32.45 ± 0.43 mV, EE of 89.1 ± 4.6%, and cumulative drug release of 94.5 ± 1.3%. Skin deposition was significantly greater (82.61 ± 1.86%) than that of the unmodified extract gel. In vivo, the phytosome gel reduced imiquimod induced psoriasis severity, demonstrating efficacy comparable to that of the reference formulation. Overall, the Leucas aspera phytosome gel significantly improved dermal delivery and therapeutic efficacy, highlighting phytosomal systems as a promising platform for topical psoriasis therapy.