Colon-adhesive poly(maleic anhydride)-sirolimus conjugate alleviates local colitis inflammation

IF 2.7 3区 化学 Q2 POLYMER SCIENCE Journal of Applied Polymer Science Pub Date : 2024-09-04 DOI:10.1002/app.56220
Sang-Hun Choi, Soo-Hyang Chi, Yu-Seong Park, Sejin Son, Young-Eun Cho, Jihoon Kim
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Abstract

Ulcerative colitis (UC) is a chronic, recurring inflammatory condition triggered by immunological imbalances in the digestive tract, leading to weight loss, diarrhea, rectal bleeding, and an increased risk of colon cancer. Existing UC treatments encounter significant limitations, such as primary non-responsiveness, secondary loss of efficacy, and adverse effects. This necessitates the development of drugs and drug formulations to broaden UC treatment options. This study describes the extended retention of poly(maleic anhydride)-drug conjugates in the large intestine of a DSS-induced acute colitis mouse model and highlights their potential for treating UC. Anti-inflammatory sirolimus (Siro) is considered an alternative drug for UC treatment, which however also has side effects due to nonspecific systemic delivery. Accordingly, poly(malic anhydride)-sirolimus (pSiro) is synthesized by linking Siro, a representative immunosuppressant and anti-inflammatory drug used in clinical practice, to anhydride groups of poly(maleic anhydride) via ester bonds. In a biodistribution study, poly(maleic anhydride) increases drug retention in the large intestine. Histochemical staining reveals the reduced inflammation degree in the treatment of pSiro, which leads to the decline of systemic inflammatory markers such as plasma TNF-α, NO, and LPS levels. These results suggest pSiro as a potential therapeutic option for the treatment of UC.

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结肠黏附性聚(马来酸酐)-西罗莫司共轭物可缓解局部结肠炎炎症
溃疡性结肠炎(UC)是一种慢性、反复发作的炎症,由消化道免疫失衡引发,导致体重减轻、腹泻、直肠出血和结肠癌风险增加。现有的 UC 治疗方法存在很大的局限性,如原发性无应答、继发性疗效丧失和不良反应。因此,有必要开发药物和药物制剂,以扩大 UC 治疗的选择范围。本研究描述了聚(马来酸酐)-药物共轭物在DSS诱导的急性结肠炎小鼠模型的大肠中的延长保留时间,并强调了其治疗UC的潜力。抗炎药西罗莫司(Siro)被认为是治疗慢性结肠炎的替代药物,但它也会因非特异性全身给药而产生副作用。因此,聚(马来酸酐)-西罗莫司(pSiro)通过酯键与聚(马来酸酐)的酸酐基团连接合成,西罗是临床上使用的一种代表性免疫抑制剂和抗炎药物。在一项生物分布研究中,聚马来酸酐增加了药物在大肠中的滞留。组织化学染色显示,使用 pSiro 治疗后炎症程度降低,从而导致全身炎症指标(如血浆 TNF-α、NO 和 LPS 水平)下降。这些结果表明 pSiro 是治疗 UC 的一种潜在疗法。
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来源期刊
Journal of Applied Polymer Science
Journal of Applied Polymer Science 化学-高分子科学
CiteScore
5.70
自引率
10.00%
发文量
1280
审稿时长
2.7 months
期刊介绍: The Journal of Applied Polymer Science is the largest peer-reviewed publication in polymers, #3 by total citations, and features results with real-world impact on membranes, polysaccharides, and much more.
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