Full-course inhibition of biodegradation-induced inflammation in fibrous scaffold by loading enzyme-sensitive prodrug
Full-course inhibition of biodegradation-induced inflammation in fibrous scaffold by loading enzyme-sensitive prodrug
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通过负载酶敏感前药全程抑制纤维支架中生物降解引起的炎症
DOI：
10.1016/j.biomaterials.2015.02.078
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发表时间：
2015-06-01
期刊：
影响因子：
14
通讯作者：
Cui, Wenguo
中科院分区：
文献类型：
--
作者：
Pan, Guoqing;Liu, Shen;Cui, Wenguo
生物降解性支架材料中的生物降解诱导的炎症是一个有待解决的关键问题，因为它可能诱导组织坏死、肉芽肿或肿瘤发生。在这里，通过简单地将酯酶敏感性前药加载到纤维支架中，证明了按需释放抗炎药物和全程抑制降解诱导的炎症的简单策略。在这项研究中，药物从载药前体支架释放显示出酶触发释放过程，这导致抗炎药物的初始适度释放和后期降解同步药物释放。这种独特的释放动力学巧妙地实现了按需药物治疗和在体内生物降解过程中有效抑制炎症。更重要的是，用不同的生物可降解聚合物制备的负载前药的支架（即，不同生物降解速率）均表现出与体内生物降解速率相匹配的药物释放动力学和对炎症的全程抑制。因此，这种方法提供了一种通用的方法，用于按需释放抗炎药物和有效抑制炎症的整个生物降解的不同聚合物支架。此外，在我们的系统中的释放动力学显示了潜在的“批量释放”的多种药物的联合治疗，以及提供了一个可行的提示，药物治疗的一些其他症状引起的体内生物降解。(C)2015爱思唯尔有限公司版权所有。
Biodegradation-induced inflammation in biodegradable scaffold materials is a critical problem to be addressed due to its potential inducement to tissue necrosis, granulomas, or tumor genesis. Here, a facile strategy for on-demand release of anti-inflammatory drugs and full-course inhibition of degradation-induced inflammation was demonstrated by simply loading an esterase-sensitive prodrug into a fibrous scaffold. In this study, drug release from the prodrug-loaded scaffolds showed an enzyme-triggered release process, which led to an initial moderate release of anti-inflammatory drugs and a later-stage degradation-synchronized drug release. This unique release kinetics ingeniously achieved on-demand drug therapy and efficient inhibition of inflammation throughout the biodegradation in vivo. More importantly, the prodrug-loaded scaffolds prepared with different biodegradable polymers (i.e., different biodegradation rates) all showed drug release kinetics that matched to the biodegradation rates and full-course inhibition of inflammation in vivo. Therefore, this method offered a general approach for on-demand release of anti-inflammatory drugs and efficient inhibition of inflammation throughout the biodegradation of different polymeric scaffolds. In addition, the release kinetics in our system showed potentials for "batch release" of multiple drugs in combination therapies as well as provided a feasible hint for the drug therapies of some other symptoms caused by in vivo biodegradation. (C) 2015 Elsevier Ltd. All rights reserved.