Hyaluronic Acid-Based Dissolving Microneedle Patch Loaded with Methotrexate for Improved Treatment of Psoriasis
Hyaluronic Acid-Based Dissolving Microneedle Patch Loaded with Methotrexate for Improved Treatment of Psoriasis
复制标题
载有甲氨蝶呤的透明质酸溶解微针贴片可改善银屑病的治疗
DOI：
10.1021/acsami.9b15668
复制
发表时间：
2019-11-20
影响因子：
9.5
通讯作者：
Tao, Juan
中科院分区：
文献类型：
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作者：
Du, Hongyao;Liu, Pei;Tao, Juan
甲氨蝶呤（MTX）是治疗中重度银屑病的一线药物之一，但注射和口服MTX引起的副作用极大地限制了其临床应用。经皮给药是一种理想的替代传统给药方法，但目前可用的皮肤渗透增强技术的性能并不令人满意。为了解决这些局限性，我们开发了一种由透明质酸（HA）制成的溶解性微针（MN）贴片，该贴片具有优异的水溶性、生物相容性、生物降解性和机械性能。可以在制造过程中控制贴片针中包封的MTX的量以获得精确的剂量。有趣的是，MTX负载的MN成功地穿透了咪喹莫特（IMQ）诱导的小鼠增厚的表皮，并在病灶内递送药物。同时，HA的快速溶解赋予了MN对患者的可操作性。我们发现载MTX的MN不仅在体外表现出良好的抑制作用，而且在小鼠中也减轻了银屑病样皮肤炎症。此外，MTX负载的MN比口服相同剂量的药物显著更有效。因此，需要更高的口服剂量的MTX才能获得相当的改善，这反过来又增加了其全身毒性。总之，提出的MTX负载溶解MN贴剂策略为有效和安全治疗银屑病提供了新的机会。
Methotrexate (MTX) is one of the first-line treatments for moderate to severe psoriasis, while the side effects caused by injection and oral administration of MTX greatly restrict its clinical application. Transdermal drug delivery offers a desirable alternative to the conventional approaches, but the performances of the currently available skin penetration enhancement techniques are not so satisfactory. To address these limitations, we developed a dissolving microneedle (MN) patch made of hyaluronic acid (HA) with excellent water solubility, biocompatibility, biodegradability, and mechanical properties. The amount of MTX encapsulated in the needles of the patch could be controlled during the fabrication process for precise dosage. Interestingly, the MTX-loaded MNs successfully penetrated imiquimod (IMQ)-induced thickened epidermis in mice and delivered the drug intralesionally. Meanwhile, fast dissolution of HA endowed the MNs with operability for patients. We found that the MTX-loaded MNs not only showed well-maintained inhibitory effect in vitro but also alleviated the psoriasis-like skin inflammation in mice. Moreover, the MTX-loaded MNs were significantly more efficacious than taking the same dose of drug orally. Consequently, a higher oral dose of MTX was required for a comparable amelioration, which in turn increased its systemic toxicity. Taken together, the proposed MTX-loaded dissolving MN patch strategy provides a new opportunity for efficient and safe treatment of psoriasis.