Arsenic trioxide liposome gels for the treatment of psoriasis in mice

Abstract

Psoriasis is a chronic, immune-mediated skin disease with no cure. Intravenous arsenic trioxide (ATO) has been used to treat psoriasis in animal studies. However, the high toxicity of ATO limits its application to clinics for systemic administration. The aim of this study was to fabricate sustained-release ATO liposome gels (ATO-Lip-Gels) to be used for the treatment of psoriasis. The ATO Liposomes were prepared using a zinc acetate gradient method. ATO concentrations were analyzed by HPLC-HG-AFS. The ATO-Lip-Gels were characterized with respect to size, zeta potential, and entrapment efficiency. Stability, in vitro drug release, and in vivo efficacy were also evaluated. The optimal formulation of ATO-Lip was ATO (0.45%), S100 (9%), and cholesterol (1.5%) (W/V) in 0.3 mol/L zinc acetate and incubated for 10 min. In the in vitro drug release study, ATO-Lip-Gels exhibited a slower release profile of ATO than that from Gels only. Compared with the model group, ATO-Lip-Gels-H significantly reduced PASI scores after psoriasis in mice and was superior to tacrolimus at day 5. HE staining showed that the pathological changes caused by psoriasis in mice were significantly improved in the treatment groups, and ATO-Lip-Gels-H had the best effect among the treatment groups. ATO-Lip-Gels applied topologically to imiquimote-induced psoriatic plaque models significantly reduced the levels of key psoriatic cytokines such as IL-6 and TNF-α. We have developed ATO-Lip-Gels for the treatment of psoriasis, which demonstrated higher efficacy with the benchmark, Tacrolimus, and can be an alternative to the conventional treatment with Tacrolimus.

Keywords:

• Arsenic trioxide
• liposomes
• gels
• psoriasis

Authors’ contributions

Liang Liu: Conceptualization, Methodology, Writing-Original draft preparation. Fengqi Ji: Conceptualization, Methodology, Data curation. Yilei Zhao: Supervision, Software, Validation. Xin Hai: Supervision, Writing- Reviewing and Editing.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Data availability

Data will be made available on request.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (No. 82274028), the Heilongjiang Key R&D Program (No. 2022ZX02C09), the Excellent Youth Foundation of First Affiliated Hospital of Harbin Medical University (No. HYD2020JQ0018), the Heilongjiang Postdoctoral Program (No. LBH-Q20031), the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province (No. CXPJJH122002-018), and the Bethune Charitable Foundation (No. Z04JKM2021005).