期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms22115433
关键词
bioachanin A; PLA-PEG-heparin; layered double hydroxide nanoparticles; controlled release; stent thrombosis; drug-eluting stent
Drug-eluting stents are widely used to prevent neointimal hyperplasia, and new coatings using herbal anti-proliferative agents and heparin-tagged polymers offer non-thrombogenic properties, sustained drug release, and complete degradation within 14 weeks.
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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