Wang Hee Lee ¹, Jun Gi Rho ^{1 2}, Yeyoung Yang ¹, Seulbi Lee ¹, Sohui Kweon ¹, Hyung-Mo Kim ³, Juhwan Yoon ¹, Hongseo Choi ¹, Eunyoung Lee ¹, Su Ha Kim ¹, Sohee You ¹, Yujin Song ¹, Young Soo Oh ⁴, Hwan Kim ⁵, Hwa Seung Han ^{6 7}, Ji Hye Han ¹, Myeongwoo Jung ⁸, Young Hwan Park ³, Yang Seon Choi ¹, Sukyoung Han ⁸, Junho Lee ², Sangdun Choi ¹, Jung-Woong Kim ⁹, Jae Hyung Park ^{6 10}, Eun Kyung Lee ⁸, Woo Keun Song ⁴, Eunha Kim ¹, Wook Kim ¹

¹Department of Molecular Science & Technology, Ajou University, Suwon16499, Republic of Korea.
²Pharmaceutical Institute, FromBIO, Suwon16681, Republic of Korea.
³KIURI Research Center, Ajou University, Suwon16499, Republic of Korea.
⁴Cell Logistics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju61005, Republic of Korea.
⁵GIST Central Research Facilities, Bio Imaging Laboratory, Gwangju Institute of Science and Technology, Gwangju61005, Republic of Korea.
⁶School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon16419, Republic of Korea.
⁷Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung25451, Republic of Korea.
⁸Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul06591, Republic of Korea.
⁹Department of Life Science, Chung-Ang University, Seoul06974, Republic of Korea.
¹⁰Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon16419, Republic of Korea.

W.H.L., J.G.R., and Y.Y. contributed equally to this work.
Corresponding Authors : Wook Kim, Eunha Kim

Although conventional topical approaches for treating psoriasis have been offered as an alternative, there are still unmet medical needs such as low skin-penetrating efficacy and off-target adverse effects. A hyaluronic acid nanoparticle (HA-NP) formed by self-assembly of HA-hydrophobic moiety conjugates has been broadly studied as a nanocarrier for long-term and target-specific delivery of drugs, owing to their excellent physicochemical and biological characteristics. Here, we identify HA-NPs as topical therapeutics for treating psoriasis using in vivo skin penetration studies and psoriasis animal models. Transcutaneously administered HA-NPs were found to be accumulated and associated with pro-inflammatory macrophages in the inflamed dermis of a psoriasis mouse model. Importantly, HA-NP exerted potent therapeutic efficacy against psoriasis-like skin dermatitis in a size-dependent manner by suppressing innate immune responses and restoring skin barrier function without overt toxicity signs. The therapeutic efficacy of HA-NPs on psoriasis-like skin dermatitis was due to the outermost hydrophilic HA shell layer of HA-NPs, independent of the molecular weight of HA and hydrophobic moiety, and comparable with that of other conventional psoriasis therapeutics widely used in the clinical settings. Overall, HA-NPs have the potential as a topical nanomedicine for treating psoriasis effectively and safely.