Abstract Based on the severity of the disease progression, the treatment of ulcerative colitis involves administration of single or multiple therapeutic agents. In refractory cases of ulcerative colitis, FK506 (FK) is the drug of choice in clinics. To maintain a long-term stable blood concentration of FK and to reduce its dosing frequency, we propose single-dose injection of FK-loaded biodegradable microspheres (FK-Ms). FK-Ms were intraperitoneally-injected into mice fed with dextran-sulfate sodium (DSS). Pharmacokinetics study revealed presence of FK in blood for over 20 days. The single intraperitoneal injection of the drug-loaded microspheres effectively alleviated DSS-induced murine colitis. Mechanistically, the single injection of FK-Ms inhibited the infiltration of T cells into colon and attenuated differentiation of T cells into interferon-γ secreting Th1 and interleukin-17A secreting Th17 cells in colon-draining mesenteric lymph nodes. Therefore, administration of prolonged-release type microspheres can be considered as an alternative for the effective treatment of inflammatory bowel diseases.

中文翻译：

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单剂量腹膜内递送 FK506 包裹的聚合物微球以减轻小鼠结肠炎

摘要 基于疾病进展的严重程度，溃疡性结肠炎的治疗涉及施用单一或多种治疗剂。在难治性溃疡性结肠炎病例中，FK506（FK）是临床上的首选药物。为了保持 FK 的长期稳定血药浓度并降低其给药频率，我们建议单剂量注射装载 FK 的可生物降解微球 (FK-Ms)。FK-Ms 被腹膜内注射到用葡聚糖-硫酸钠 (DSS) 喂养的小鼠体内。药代动力学研究表明，血液中存在 FK 超过 20 天。单次腹腔注射载药微球可有效缓解 DSS 诱导的小鼠结肠炎。从机制上讲，单次注射 FK-Ms 抑制了 T 细胞向结肠的浸润，并减弱了 T 细胞向结肠引流肠系膜淋巴结中分泌干扰素-γ 的 Th1 和分泌白细胞介素-17A 的 Th17 细胞的分化。因此，可以考虑使用缓释型微球作为有效治疗炎症性肠病的替代方案。