Construction of IL-2 Sustained-Release Polysaccharide Hydrogel and Amelioration of Sjögren's Syndrome in a Murine Model.

OBJECTIVE

This study aimed to fabricate an injectable interleukin-2 (IL-2)-loaded chitosan hydrogel capable of sustained drug release, and explore its capacity to restore immune homeostasis in a murine Sjögren's syndrome model.

METHODS

Injectable cellulose acetoacetate-chitosan (CAA-CS) hydrogels were fabricated via dynamic enamine crosslinking and loaded with recombinant IL-2 to achieve sustained drug release. The physicochemical properties and biocompatibility of the hydrogels were systematically characterized. Furthermore, the in vivo pharmacokinetic behavior and therapeutic efficacy of the optimized hydrogel were evaluated in a murine Sjögren's syndrome model.

RESULTS

The CAA-CS hydrogel possessed good biocompatibility and sustained protein release over 144 h. It significantly extended IL-2 plasma elimination half-life (P < 0.001). In NOD mice, the IL-2-loaded hydrogel restored salivary secretion, lowered anti-SSA antibodies and alleviated glandular inflammation (all P < 0.05). Flow cytometry showed selective expansion of splenic Tregs, which significantly balanced abnormal Th1/Treg and Th17/Treg ratios (P < 0.001) to restore immune homeostasis.

CONCLUSION

This work successfully developed an IL-2-loaded polysaccharide hydrogel with sustained release. The formulation slows rapid IL-2 clearance and significantly optimizes its pharmacokinetic profile, correcting abnormal Th1/Treg and Th17/Treg immune ratios in a murine Sjögren's syndrome model. This polysaccharide-based delivery platform exhibits favorable translational potential for SS treatment, and the present findings confirm that rational release modulation boosts IL-2 immunotherapeutic efficacy.