European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2026
Construction of IL-2 Sustained-Release Polysaccharide Hydrogel and Amelioration of Sjögren's Syndrome in a Murine Model.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ni Xiaohan, Jin Xueyan, Jin Yue, Li Jiaqi, Liang Zhaojun, Qiang Le, Wang Yanlin, Xue Jiahui, Sun Lei, Zhong Yi, Luo Jing
Аннотация
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.
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.