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.

Cold-active lipases are gaining special attention nowadays as they are increasingly used in various industries such as fine chemical synthesis, food processing, and washer detergent. In the present study, an extracellular lipase gene from Yarrowia lipolytica (LIPY8) was cloned and expressed by baculovirus expression system. The recombinant lipase (LipY8p) was purified using chromatographic techniques, resulting in a purification factor of 25.7-fold with a specific activity of 1102.9U/mg toward olive oil. The apparent molecular mass of purified LipY8p was 40 kDa. The enzyme was most active at pH 7.5 and 17 °C. It exhibited maximum activity toward medium chain (C10) esters. The presence of transition metals such as Zn2+, Cu2+, and Ni2+ strongly inhibited the enzyme activity, which was enhanced by EDTA. The lipase activity was affected by detergents and was elevated by various organic solvents at 10% (v/v). These enzymatic properties make this lipase of considerable potential for biotechnological applications.