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.

银屑病关节炎（PsA）是一种复杂的牛皮癣合并症，表现为银屑病皮肤和关节炎性关节，为同时向PsA中的不同作用部位同时递送不同药物的量身定制特殊的治疗策略仍然具有挑战性。我们开发了一种基于需求的分层溶解微针（MN）系统，该系统在MN的不同层（即TD-MN ）中加载了免疫抑制剂他克莫司（TAC）和抗炎双氯芬酸（DIC），旨在将TAC和DIC专门递送至皮肤和关节腔，同时减轻PsA中的牛皮癣皮肤和关节炎性关节病变。在 体外和体内皮肤渗透表明，夹层将TAC保留在约100μm的皮肤内，而尖端层将DIC输送的约300μm保留在关节腔内。TD-MN不仅有效地减少了牛皮癣面积和严重程度指数，并恢复了咪喹莫特诱发的牛皮癣的增厚表皮，而且通过减少关节肿胀，肌肉萎缩和软骨破坏，甚至比DIC注射更好地减轻了角叉菜胶/高岭土引起的关节炎。重要的是，TD-MN在银屑病和关节炎大鼠中显着抑制血清TNF - α和IL-17A。结果证明该方法代表了多种药物合并治疗的有前途的替代方法，为满足PsA治疗的需求提供了方便有效的策略。