Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis.
Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis.
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DOI：
10.1016/j.apsb.2020.08.008
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Yu K;Yu X;Cao S;Wang Y;Zhai Y;Yang F;Yang X;Lu Y;Wu C;Xu Y
银屑病关节炎（PsA）是一种复杂的银屑病合并症，具有银屑病皮肤和关节炎关节的表现，并且定制特定的治疗策略以同时将不同的药物递送到PsA的不同作用部位仍然具有挑战性。我们开发了一种基于需要的分层溶解微针（MN）系统，在MN的不同层中加载免疫抑制剂他克莫司（TAC）和抗炎剂双氯芬酸（DIC），即，TD-MN旨在将TAC和DIC特异性递送至皮肤和关节腔，实现同时缓解PsA中的银屑病皮肤和关节炎关节病变。体外和体内皮肤渗透实验表明，中间层将TAC保留在皮肤内约100 μm，而尖端层将DIC递送到关节腔中约300 μm。TD-MN不仅有效地减少银屑病面积和严重程度指数评分，并恢复咪喹莫特诱导的银屑病增厚的表皮，而且通过减少关节肿胀、肌肉萎缩和软骨破坏，减轻角叉菜胶/高岭土诱导的关节炎甚至比DIC注射剂更好。TD-MN对银屑病和关节炎大鼠血清TNF-α和IL-17 A的影响显著。结果支持，这种方法是一种有前途的替代多种不同药物的合并症，提供了一个方便和有效的策略，以满足PsA治疗的要求。一种基于针的分层溶解微针系统，在不同层中负载他克莫司（TAC）和双氯芬酸钠（DIC），将TAC和DIC特异性地递送至皮肤和关节腔，同时缓解银屑病皮肤和关节炎关节病变。
Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs, i.e., TD-MN, which aims to specifically deliver TAC and DIC to skin and articular cavity, achieving simultaneous alleviation of psoriatic skin and arthritic joint lesions in PsA. In vitro and in vivo skin permeation demonstrated that the inter-layer retained TAC within the skin of ∼100 μm, while the tip-layer delivered DIC up to ∼300 μm into the articular cavity. TD-MN not only efficiently decreased the psoriasis area and severity index scores and recovered the thickened epidermis of imiquimod-induced psoriasis but also alleviated carrageenan/kaolin-induced arthritis even better than DIC injection through reducing joint swelling, muscle atrophy, and cartilage destruction. Importantly, TD-MN significantly inhibited the serum TNF-α and IL-17A in psoriatic and arthritic rats. The results support that this approach represents a promising alternative to multi-administration of different drugs for comorbidity, providing a convenient and effective strategy for meeting the requirements of PsA treatment. A need-based layered dissolving microneedle system loading tacrolimus (TAC) and diclofenac sodium (DIC) in different layers specifically delivers TAC and DIC to skin and articular cavity, simultaneously alleviating psoriatic skin and arthritic joint lesions.
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DOI：
10.4049/jimmunol.181.7.4733
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
通讯作者：
Zou W
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影响因子：
9.5
作者：
Du, Hongyao;Liu, Pei;Tao, Juan
通讯作者：
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影响因子：
6.5
作者：
Chiricozzi, Andrea;Guttman-Yassky, Emma;Krueger, James G.
通讯作者：
Krueger, James G.
影响因子：
4.4
作者：
Hartupee, Justin;Liu, Caini;Hamilton, Thomas
通讯作者：
Hamilton, Thomas
DOI：
10.1073/pnas.1917891117
发表时间：
2020-02-18
影响因子：
11.1
作者：
Chen, Guojun;Chen, Zhitong;Gu, Zhen
通讯作者：
Gu, Zhen