Yang Mai, Yaqi Ouyang, Mian Yu, Yujia Qin, Michael Girardi, W Mark Saltzman, Emiliano Cocco, Chao Zhao, Liu Yu, Yizhen Jia, Lingyun Xiao, Liu Dou, Wenbin Deng, Yang Liu, Julin Xie, Yang Deng

First-line treatments for mild to moderate psoriasis are typically topical formulations containing corticosteroids, however, the therapeutic efficacy of these formulations is compromised by limited penetration and skin retention. Even more challenging, off-target corticosteroids are known to adversely affect healthy skin, including induction of epidermal and dermal atrophy. Here, we report a nanoparticle-based topical formulation that cures psoriasis in a single dose, but leaves healthy skin intact. Specifically, we developed tris(hydroxymethyl)aminomethane-modified bioadhesive nanoparticles (Tris-BNPs) that exploit the high permeability characteristic of psoriasis to penetrate only psoriatic skin but not the healthy skin. Furthermore, as Tris-BNPs diffuse and penetrate into the epidermis, the Tris molecules slowly diffuse away, exposing the aldehyde groups of BNPs, which can bind to amine groups present within lesional skin, leading to long local retention of BNPs in lesions of psoriatic skin. The accumulated BNPs within lesions release corticosteroids over a ~ 3 day period to maintain local drug concentration above the therapeutic level. In addition to deeper penetration and longer retention compared with commercial psoriasis treatments, the topical applied Tris-BNPs were not affected by sweating, humidity, or active wiping due to their preferential accumulation between the stratum corneum and the basal cells of the epidermis. Overall, Tris-BNP as a topical formulation hold promise to overcome the limitations of current psoriasis treatment.