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肝素化 PLA-PEG 嵌段共聚物包裹的芒柄花素载入(Mg/Al)层状双氢氧化物纳米粒子,有望成为非血栓形成和抗增殖支架涂层。

Heparin-Tagged PLA-PEG Copolymer-Encapsulated Biochanin A-Loaded (Mg/Al) LDH Nanoparticles Recommended for Non-Thrombogenic and Anti-Proliferative Stent Coating.

机构信息

Center for Nanofibers and Nanotechnology, National University of Singapore, Singapore 119260, Singapore.

Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, China.

出版信息

Int J Mol Sci. 2021 May 21;22(11):5433. doi: 10.3390/ijms22115433.

Abstract

Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs suffer from stent thrombosis due to the non-selective nature of the drugs and hypersensitivity to polymer degradation products. Alternatively, various herbal anti-proliferative agents are sought, of which biochanin A (an isoflavone phytoestrogen) was known to have anti-proliferative and vasculoprotective action. PLA-PEG diblock copolymer was tagged with heparin, whose degradation releases heparin locally and prevents thrombosis. To get a controlled drug release, biochanin A was loaded in layered double hydroxide nanoparticles (LDH), which are further encapsulated in a heparin-tagged PLA-PEG copolymer. LDH nanoparticles are synthesized by a co-precipitation process; in situ as well as ex situ loading of biochanin A were done. PLA-PEG-heparin copolymer was synthesized by esterification reaction, and the drug-loaded nanoparticles are coated. The formulation was characterized by FTIR, XRD, DSC, DLS, and TEM. In vitro drug release studies, protein adhesion, wettability, hemocompatibility, and degradation studies were performed. The drug release was modeled by mathematical models to further emphasize the mechanism of drug release. The developed drug-eluting stent coating is non-thrombogenic, and it offers close to zero-order release for 40 days, with complete polymer degradation in 14 weeks.

摘要

药物洗脱支架已广泛用于预防与裸金属支架相关的新生内膜增生。由于药物的非选择性和对聚合物降解产物的过敏,传统的聚合物和抗增殖药物会导致支架血栓形成。另一方面,人们在寻找各种草药抗增殖剂,其中生物素 A(一种异黄酮植物雌激素)具有抗增殖和血管保护作用。PLA-PEG 嵌段共聚物与肝素结合,肝素的降解会局部释放肝素,从而防止血栓形成。为了实现药物的控制释放,将生物素 A 载入层状双氢氧化物纳米粒子(LDH)中,然后将其进一步封装在肝素标记的 PLA-PEG 共聚物中。LDH 纳米粒子通过共沉淀法合成;进行了原位和异位加载生物素 A。通过酯化反应合成 PLA-PEG-肝素共聚物,并对载药纳米粒子进行包衣。通过傅里叶变换红外光谱(FTIR)、X 射线衍射(XRD)、差示扫描量热法(DSC)、动态光散射(DLS)和透射电子显微镜(TEM)对制剂进行了表征。进行了体外药物释放研究、蛋白质黏附、润湿性、血液相容性和降解研究。通过数学模型对药物释放进行建模,以进一步强调药物释放的机制。开发的药物洗脱支架涂层具有抗血栓形成性,可在 40 天内接近零级释放,并在 14 周内完全降解聚合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5093/8196732/4844047dd6fa/ijms-22-05433-g001.jpg

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