The proper storage temperature of dissolving insulin microneedles (INS MNs) is crucial for their clinical application to prevent insulin inactivation. This study aims to explore the impact of temperature on the dissolving INS MNs and offer appropriate storage recommendations. Two commonly clinical utilized materials, hyaluronic acid (HA) and polyvinyl alcohol (PVA), were selected for fabricating four kinds of microneedles to examine the stability of these MNs concerning molecular weight and adjuvant sucrose: PVA MNs, PVA with Sucrose MNs (PVA-S MNs), HA with molecular weights of 8 kDa and 160 kDa MNs (HA0.8 and HA16 MNs). The drug stability of these INS MNs was assessed at storage temperatures of 4℃, 25℃, 40℃, and 60℃ utilizing electron microscopy (EM), scanning electron microscope (SEM), circular dichroism (CD), and molecular dynamics (MD) simulation. Experimental results revealed that all four types of dissolving INS MNs remained stable for a minimum of 6 months when stored at 4℃. The inclusion of sucrose has been shown to enhance the structural stability of INS MN at both 4°C and 25°C temperatures. Furthermore, microneedles loaded with insulin in a soluble form demonstrated superior stability compared to insulin solutions. Based on these results, tailored storage recommendations were provided for each type of dissolving INS MNs. In summary, the broad storage temperature range for dissolving INS MNs not only reduces the costs associated with insulin 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.