Increased Anti‐Psoriatic Effect of Anti‐Inflammatory Dendrimers Using Fluid Catanionic Vesicle‐Based Topical Formulations

Psoriasis is a chronic inflammatory skin disease requiring effective anti‐inflammatory treatments. The IMD‐006 dendrimer exhibits promising immunomodulatory effects, but optimized formulations are needed to improve skin penetration. This study describes fluid vesicle formulations to enhance IMD‐006 delivery and evaluates their anti‐psoriatic efficacy in a murine model, offering potential for innovative topical therapies. Due to IMD‐006 ’s hydrolytic instability at pH 7, more stable analogues, IMD‐036 and IMD‐046 , are designed with phosphoramidate and triazine branching points, improving hydrolytic resistance. Fluorescent derivatives are also synthesized using copper‐free click chemistry for biological studies. These dendrimers are actively internalized by monocytes, promoting an anti‐inflammatory phenotype. Encapsulation in highly fluid TriCat catanionic vesicles significantly enhances cellular uptake and skin penetration, particularly for IMD‐006 and IMD‐036 , facilitating deeper tissue diffusion without systemic exposure. A xanthan‐based hydrogel incorporating TriCat vesicles loaded with these dendrimers is developed for topical application, improving stability, sustained drug release, and skin permeability. In a psoriatic mouse model, TriCat/IMD‐006 and TriCat/IMD‐036 formulations significantly reduced disease severity ( p < 0.0001 and p < 0.05 respectively), producing clinical and histopathological outcomes equivalent to corticosteroid treatment. These findings highlight the potential of dendrimer‐based formulations as effective topical treatments for psoriasis, offering an alternative to conventional corticosteroids.