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Heparin-Coated Albumin Nanoparticles for Drug Combination in Targeting Inflamed Intestine.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-06-29 , DOI: 10.1002/adhm.202000536 Sufeng Zhang 1, 2, 3 , Won Joon Cho 2 , Amy T Jin 1, 2 , Lie Yun Kok 2 , Yunhua Shi 2 , David E Heller 2 , Young-Ah Lucy Lee 2 , Yixuan Zhou 2 , Xi Xie 2 , Joshua R Korzenik 1, 3 , Jochen K Lennerz 3, 4 , Giovanni Traverso 1, 3, 5
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-06-29 , DOI: 10.1002/adhm.202000536 Sufeng Zhang 1, 2, 3 , Won Joon Cho 2 , Amy T Jin 1, 2 , Lie Yun Kok 2 , Yunhua Shi 2 , David E Heller 2 , Young-Ah Lucy Lee 2 , Yixuan Zhou 2 , Xi Xie 2 , Joshua R Korzenik 1, 3 , Jochen K Lennerz 3, 4 , Giovanni Traverso 1, 3, 5
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Targeting areas of inflammation offers potential therapeutic and diagnostic benefits by maximizing drug and imaging marker on‐target effects while minimizing systemic exposure that can be associated with adverse side effects. This strategy is particularly beneficial in the management of inflammatory bowel disease (IBD). Here an inflammation‐targeting (IT) approach based on heparin‐coated human serum albumin nanoparticles (HEP‐HSA NPs) that utilize the increased intestinal permeability and changes in electrostatic interaction at the site of intestinal inflammation is described. Using small‐molecule and biologic drugs as a model for drug combination, the HEP‐HSA NPs demonstrate the capacity to load both drugs simultaneously; the dual‐drug loaded HEP‐HSA NPs exhibit a higher anti‐inflammatory effect than both of the single‐drug loaded NPs in vitro and selectively bind to inflamed intestine after enema administration in vivo in a murine model of colitis. Importantly, analyses of the physicochemical characteristics and targeting capacities of these NPs indicate that HEP coating modulates NP binding to the inflamed intestine, providing a foundation for future IT‐NP formulation development.
中文翻译：
肝素包被的白蛋白纳米颗粒用于靶向发炎肠道的药物组合。
通过最大限度地提高药物和成像标记物的靶向效果，同时最大限度地减少可能与不良副作用相关的全身暴露，靶向炎症区域可提供潜在的治疗和诊断益处。该策略对于炎症性肠病（IBD）的治疗特别有益。这里描述了一种基于肝素包被的人血清白蛋白纳米颗粒（HEP-HSA NP）的炎症靶向（IT）方法，该方法利用肠道通透性的增加和肠道炎症部位静电相互作用的变化。使用小分子和生物药物作为药物组合的模型，HEP-HSA NPs 表现出同时负载两种药物的能力；双药负载的 HEP-HSA NPs 在体外表现出比两种单药负载的 NPs 更高的抗炎作用，并且在小鼠结肠炎模型中体内灌肠后选择性地结合到发炎的肠道。重要的是，对这些 NP 的理化特性和靶向能力的分析表明，HEP 涂层可调节 NP 与发炎肠道的结合，为未来 IT-NP 制剂的开发奠定了基础。
更新日期：2020-08-19
中文翻译：
肝素包被的白蛋白纳米颗粒用于靶向发炎肠道的药物组合。
通过最大限度地提高药物和成像标记物的靶向效果，同时最大限度地减少可能与不良副作用相关的全身暴露，靶向炎症区域可提供潜在的治疗和诊断益处。该策略对于炎症性肠病（IBD）的治疗特别有益。这里描述了一种基于肝素包被的人血清白蛋白纳米颗粒（HEP-HSA NP）的炎症靶向（IT）方法，该方法利用肠道通透性的增加和肠道炎症部位静电相互作用的变化。使用小分子和生物药物作为药物组合的模型，HEP-HSA NPs 表现出同时负载两种药物的能力；双药负载的 HEP-HSA NPs 在体外表现出比两种单药负载的 NPs 更高的抗炎作用，并且在小鼠结肠炎模型中体内灌肠后选择性地结合到发炎的肠道。重要的是，对这些 NP 的理化特性和靶向能力的分析表明，HEP 涂层可调节 NP 与发炎肠道的结合，为未来 IT-NP 制剂的开发奠定了基础。
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