Photoinitiator-free gelatin hydrogel microneedles for acute gouty arthritis treatment

Photo-crosslinked microneedles (MNs) are widely used in biomedical applications, but their dependence on exogenous photoinitiators continues to pose a fundamental challenge to their further advancement. Herein, we have developed a hydrogel MN system loaded with self-assembled nanoparticles (NPs). The NPs are composed of natural polyphenols and indomethacin. The MN system is rapidly dissolving and is fabricated through an initiator-free photo-crosslinking process. Systematic investigation of the gel composition, swelling behavior, and mechanical properties of lipoic acid-modified gelatin (GelLA)-based MNs demonstrated both swelling and mechanical strength could be readily tuned. Notably, the tunable mechanical feature of GelLA enabled effective penetration of the stratum corneum, facilitating efficient transdermal drug delivery. Compared with gelatin methacryloyl, GelLA-based hydrogel MNs prepared at the same concentration exhibited superior biocompatibility, while eliminating the potential cytotoxicity associated with exogenous photoinitiators. Further in vivo evaluation in an acute gouty arthritis model demonstrated that the MN system could significantly alleviate joint inflammation through rapid drug release, highlighting its potent anti-inflammatory efficacy. Overall, this initiator-free, photo-crosslinkable GelLA-based MNs system offered a safe, efficient, and user-friendly strategy for local drug delivery in the management of acute gouty arthritis.