Shen Shulin, Zheng Xi, Dong Xu, Fang Min, Wan Aiqun, Zhu Tong, Yang Qingliang, Xie Jing, Yan Qinying
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China; Research Institute of Pharmaceutical Particle Technology, Zhejiang University of Technology, Hangzhou 310014, PR China.
Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University, Hangzhou 310014, PR China.
Eur J Pharm Sci. 2024 Apr 1;195:106711. doi: 10.1016/j.ejps.2024.106711. Epub 2024 Jan 28.
Methotrexate (MTX) is a first-line drug in treating psoriasis because of its strong anti-proliferation and anti-inflammatory effects. However, systemic administration of MTX will lead to many side effects, such as gastrointestinal irritation, liver and kidney toxicity, etc. Herein, we developed liposome-loaded microneedles (MNs) system to improve transdermal efficiency, which was used to overcome the problems of low transdermal efficiency and poor therapeutic effect of traditional transdermal drug delivery methods. Hyaluronic acid (HA) was modified on the surface of MTX-loaded liposomes. The interaction of HA and CD44 could increase the adhesion of HA-MTX-Lipo to HaCaT cells, thereby promoting the apoptosis or death of HaCaT cells. Results indicated HA-MTX-Lipo MNs could inhibit the development of psoriasis and reduce the degree of skin erythema, scaling, and thickening. The mRNA levels of proinflammatory cytokines such as IL-17A, IL-23, and TNF-α were decreased. The epidermal thickness and proliferative cell-associated antigen Ki67 expression were also reduced. Specifically, the expression of mRNA levels of proinflammatory cytokines was down-regulated. The MNs transdermal delivery of HA-modified-MTX liposomes provided a promising method for treating psoriasis.
甲氨蝶呤（MTX）因其强大的抗增殖和抗炎作用，是治疗银屑病的一线药物。然而，MTX的全身给药会导致许多副作用，如胃肠道刺激、肝肾毒性等。在此，我们开发了载脂质体微针（MNs）系统以提高透皮效率，用于克服传统经皮给药方法透皮效率低和治疗效果差的问题。在载MTX脂质体表面修饰了透明质酸（HA）。HA与CD44的相互作用可增加HA-MTX-Lipo与HaCaT细胞的黏附，从而促进HaCaT细胞的凋亡或死亡。结果表明，HA-MTX-Lipo MNs可抑制银屑病的发展，减轻皮肤红斑、脱屑和增厚程度。促炎细胞因子如IL-17A、IL-23和TNF-α的mRNA水平降低。表皮厚度和增殖细胞相关抗原Ki67的表达也降低。具体而言，促炎细胞因子mRNA水平的表达下调。HA修饰的MTX脂质体的MNs经皮给药为治疗银屑病提供了一种有前景的方法。
