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An injectable thermosensitive hydrogel loaded with an ancient natural drug colchicine for myocardial repair after infarction.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-01-13 , DOI: 10.1039/c9tb02523e Yu Chen 1 , Jiayue Shi 2 , Yaping Zhang 1 , Jiajun Miao 2 , Zhe Zhao 1 , Xian Jin 1 , Liang Liu 1 , Lin Yu 3 , Chengxing Shen 1 , Jiandong Ding 3
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-01-13 , DOI: 10.1039/c9tb02523e Yu Chen 1 , Jiayue Shi 2 , Yaping Zhang 1 , Jiajun Miao 2 , Zhe Zhao 1 , Xian Jin 1 , Liang Liu 1 , Lin Yu 3 , Chengxing Shen 1 , Jiandong Ding 3
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Localized administration of anti-inflammatory agents benefits patients after myocardial infarction (MI) by repressing/modulating inflammatory response of the MI region and thus accelerating repair of the impaired tissues. Colchicine (Col), an ancient natural drug, has excellent anti-inflammatory effects; however, its utilization is strictly limited due to its severe systemic toxicity and narrow therapeutic window. In this study, we developed an intramyocardial delivery system of Col using an injectable, thermosensitive poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) polymer hydrogel as the vehicle for the treatment of MI while minimizing its systemic toxicity. The aqueous PLGA-PEG-PLGA solution loaded with Col (Col@Gel) underwent a sol-gel transition at 35 °C and maintained a gel state at body temperature. Col was released from the Col@Gel in an initial burst followed by a sustained release manner for over 8 days. The in vitro cell tests showed that the Col@Gel system significantly inhibited macrophage proliferation and migration. In a mouse model of MI, a single intramyocardial administration of the Col@Gel effectively alleviated cardiac inflammation, inhibited myocardial apoptosis and fibrosis, improved cardiac function and structure, and increased mouse survival without inducing severe systemic toxicity, which was observed following intraperitoneal administration of Col solution. These results suggested that the Col@Gel system is a reliable drug delivery system for the sustained local release of Col and has great potential as an anti-inflammatory therapy for the treat of MI.
中文翻译：
一种可注射的热敏水凝胶，其中装有古老的天然药物秋水仙碱，可在梗塞后用于心肌修复。
局部施用抗炎药可通过抑制/调节MI区的炎症反应，从而加速受损组织的修复，使心肌梗塞（MI）后的患者受益。秋水仙碱（Col）是一种古老的天然药物，具有出色的抗炎作用；然而，由于其严重的全身毒性和狭窄的治疗窗口，其使用受到严格限制。在这项研究中，我们使用可注射的热敏聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯（PLGA-PEG-PLGA）聚合物水凝胶开发了Col的心肌内递送系统用于治疗MI的载体，同时将其全身毒性降至最低。负载有Col（Col @ Gel）的PLGA-PEG-PLGA水溶液在35℃下经历溶胶-凝胶转变，并在体温下保持凝胶状态。Col在最初的爆发中从Col @ Gel中释放出来，然后持续释放超过8天。体外细胞测试表明，Col @ Gel系统显着抑制了巨噬细胞的增殖和迁移。在心肌梗死的小鼠模型中，Col @ Gel的单次心肌内给药可有效缓解心脏炎症，抑制心肌细胞凋亡和纤维化，改善心脏功能和结构，并增加小鼠存活率，而不会引起严重的全身毒性，这在腹膜内给药后可观察到。彻尔溶液。
更新日期：2020-02-13
中文翻译：
一种可注射的热敏水凝胶，其中装有古老的天然药物秋水仙碱，可在梗塞后用于心肌修复。
局部施用抗炎药可通过抑制/调节MI区的炎症反应，从而加速受损组织的修复，使心肌梗塞（MI）后的患者受益。秋水仙碱（Col）是一种古老的天然药物，具有出色的抗炎作用；然而，由于其严重的全身毒性和狭窄的治疗窗口，其使用受到严格限制。在这项研究中，我们使用可注射的热敏聚丙交酯-乙交酯-聚乙二醇-聚丙交酯-乙交酯（PLGA-PEG-PLGA）聚合物水凝胶开发了Col的心肌内递送系统用于治疗MI的载体，同时将其全身毒性降至最低。负载有Col（Col @ Gel）的PLGA-PEG-PLGA水溶液在35℃下经历溶胶-凝胶转变，并在体温下保持凝胶状态。Col在最初的爆发中从Col @ Gel中释放出来，然后持续释放超过8天。体外细胞测试表明，Col @ Gel系统显着抑制了巨噬细胞的增殖和迁移。在心肌梗死的小鼠模型中，Col @ Gel的单次心肌内给药可有效缓解心脏炎症，抑制心肌细胞凋亡和纤维化，改善心脏功能和结构，并增加小鼠存活率，而不会引起严重的全身毒性，这在腹膜内给药后可观察到。彻尔溶液。
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