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Abstract：
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.
摘要：
银屑病关节炎（PsA）是一种复杂的银屑病合并症，表现为银屑病皮肤和关节炎关节，和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求的分层溶解微针（MN）系统，在不同的MN层中加载免疫抑制剂他克莫司（TAC）和抗炎双氯芬酸（DIC），即，TD-MN,旨在将TAC和DIC专门输送到皮肤和关节腔，同时减轻PsA的银屑病皮肤和关节炎关节病变。体外和体内皮肤渗透表明，中间层在皮肤内保留了100μm的TAC，而尖端层将高达300μm的DIC输送到关节腔。TD-MN不仅有效地降低了银屑病面积和严重程度指数评分，恢复了咪喹莫特诱导的银屑病表皮增厚，而且通过减少关节肿胀，甚至比注射DIC更好地减轻了角叉菜胶/高岭土诱导的关节炎。肌肉萎缩,和软骨破坏。重要的是,TD-MN对银屑病和关节炎大鼠血清TNF-α和IL-17A均有明显的抑制作用。结果支持，这种方法代表了一种有希望的替代方法，以多种药物治疗合并症，为满足PsA治疗的要求提供了一种方便有效的策略。
