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

Heparin-Tagged PLA-PEG Copolymer-Encapsulated Biochanin A-Loaded (Mg/Al) LDH Nanoparticles Recommended for Non-Thrombogenic and Anti-Proliferative Stent Coating.
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DOI:
10.3390/ijms22115433
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发表时间:
2021-05-21
影响因子:
5.6
通讯作者:
Ramakrishna S
Ramakrishna S
中科院分区:
生物学2区
文献类型:
--
作者:
Adepu S;Luo H;Ramakrishna S

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药物洗脱支架已被广泛植入,以防止与裸金属支架相关的内膜增生。由于药物的非选择性和对聚合物降解产物的超敏感性,传统聚合物和抗增殖药物容易发生支架血栓形成。另外,人们也在寻找各种草药抗增殖剂,其中生物茶素A(一种异黄酮植物雌激素)已知具有抗增殖和血管保护作用。用肝素标记PLA-PEG二嵌段共聚物,其降解可局部释放肝素,防止血栓形成。为了控制药物释放,生物茶素a被装载在层状双氢氧化物纳米颗粒(LDH)中,LDH被进一步封装在肝素标记的PLA-PEG共聚物中。采用共沉淀法合成了LDH纳米颗粒;进行了生物茶素A的原位和非原位加载。通过酯化反应合成pla - peg -肝素共聚物,并包被载药纳米颗粒。通过FTIR、XRD、DSC、DLS、TEM等手段对配方进行表征。进行了体外药物释放研究、蛋白质粘附性、润湿性、血液相容性和降解研究。采用数学模型对药物释放进行建模,进一步强调药物释放的机制。开发的药物洗脱支架涂层不会产生血栓,并且在40天内提供接近零级释放,在14周内完全降解聚合物。
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.
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