The proper storage temperature for dissolving insulin microneedles (INS MNs) is crucial for their clinical application to prevent INS inactivation. This study aimed to explore the impact of temperature on the dissolution of INS MNs and provide appropriate storage recommendations. Two commonly used materials, hyaluronic acid (HA) and polyvinyl alcohol (PVA), were selected for the fabrication of four kinds of MNs to examine the stability of these MNs with respect to molecular weight and the sucrose adjuvant: PVA MNs, PVA with sucrose MNs, and HA with molecular weights of 8 and 160 kDa MNs. The drug stability of these INS MNs was assessed at storage temperatures of 4, 25, 40, and 60°C via electron microscopy, scanning electron microscopy, circular dichroism, and molecular dynamics simulations. The experimental results revealed that all four types of dissolving INS MNs remained stable for a minimum of 6 months when stored at 4°C. The inclusion of sucrose has been shown to increase the structural stability of INS MNs at both 4 and 25°C. Furthermore, MNs loaded with INS in a soluble form demonstrated superior stability compared with those loaded with INS solutions. On the basis of these results, tailored storage recommendations were provided for each type of dissolving INS MN. In summary, the broad storage temperature range for dissolving INS MNs not only reduces the costs associated with INS transportation and storage but also offers convenience for healthcare professionals and patients.

Modulating the immune microenvironment to establish sustained positive feedback within immune pathways represents a promising avenue for the treatment of autoimmunity. However, the precise and efficient delivery of therapeutic systems to the subcutaneous basal layer to modulate immune disorders is a major challenge in the treatment of autoimmune psoriasis. In this project, we introduce a dual-functional microneedle (DF-MN) designed to combine MNs with multiple release kinetics and immunotherapy, the programmed treatment is achieved through segmented design of the MN structure, realizing the unification of rapid and long-lasting treatment of autoimmune psoriasis. In vivo imaging results showed that GelMA@M-CSF showed fluorescent signals after 5 days of delivery to subcutaneous tissues, whereas HA@IL-13 showed minimal fluorescent signals after 2 days. The multistage release behavior of MNs and the diffusion mechanism of drugs were explained at the molecular level, in combination with coarse-grained molecular dynamics. Additionally, DF-MN can successfully induce macrophage reprogramming in vitro and ameliorate overall symptoms in a psoriasis mice model, suggesting that it has the potential to be an effective strategy for the treatment of psoriasis and portends to be a transformative platform for the treatment of other autoimmune diseases.