Micelle-Embedded Layer-by-Layer Coating with Catechol and Phenylboronic Acid for Tunable Drug Loading, Sustained Release, Mild Tissue Response, and Selective Cell Fate for Re-endothelialization
Micelle-Embedded Layer-by-Layer Coating with Catechol and Phenylboronic Acid for Tunable Drug Loading, Sustained Release, Mild Tissue Response, and Selective Cell Fate for Re-endothelialization
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DOI：
10.1021/acsami.9b01253
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发表时间：
2019-03-13
影响因子：
9.5
通讯作者：
Wang, Yunbing
中科院分区：
文献类型：
--
作者：
Lu, Jiang;Zhuang, Weihua;Wang, Yunbing
可调/持续的药物装载/释放在解决生物医学应用中的低细胞毒性、长期性能和局部温和愈合反应方面具有重要意义。以壳聚糖/肝素为聚电解质，采用胶束包埋技术，在壳聚糖骨架上接枝邻苯二酚，在胶束表面修饰苯硼酸，构建了一种自修复的夹心层-逐层（LBL）涂层，通过涂层组分之间的相互作用（例如，硼酸酯键形成、弱分子间交联、π-π相互作用和H-键合）。此外，雷帕霉素和阿托伐他汀钙作为候选药物，并加载到胶束，然后药物释放行为的研究。结果发现，LBL涂层保持线性增长模式高达30个周期，给出了一个有利的可调性的涂层结构和药物负载。涂层还可以支持有效载荷的持续释放并提供野生组织响应。通过系统的体外和体内研究，这种具有药物负载的儿茶酚-苯基硼酸增强的LBL涂层还将通过调节涂层周期和负载的药物来解决增强的抗血小板粘附/活化和内皮细胞和平滑肌细胞的直接细胞命运。通过模块化组装，这种涂层显示了实现血管植入物的增强再内皮化的潜力。
Tunable/sustained drug loading/releasing are of significance in addressing low cytotoxicity, long-term performance, and localized mild healing response in biomedical applications. With an ingenious design, a self-healing sandwiched layer-by-layer (LBL) coating was constructed by using chitosan/heparin as adopted polyelectrolytes with embedding of micelles, in which the chitosan backbone was grafted with catechol and the micelle was modified with exposed phenylboronic acid, endowing the coating with enhanced stability by abundant interactions among coating components (e.g., boric acid ester bond formation, weak intermolecular cross-linking, pi-pi interactions, and H-bonding). Moreover, rapamycin and atorvastatin calcium were selected as drug candidates and loaded into micelles, followed by drug-releasing behavior study. It was found that the LBL coating maintained a linear growth mode up to 30 cycles, giving a favorable tunability of coating construction and drug loading. The coating could also support sustained release of payloads and provide wild tissue response. With the systematic in vitro and in vivo study, such catechol-phenylboronic acid-enhanced LBL coating with drug loading would also address enhanced antiplatelet adhesion/activation and direct cell fate of endothelial cells and smooth muscle cells via tuning of coating cycles and loaded drugs. With modular assembly, such coating indicated potential for achieving enhanced re-endothelialization for vascular implants.