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.

Highlights

  • The implantation of a balloon expandable stent by percutaneous coronary angioplasty is the most commonly used medical intervention to re-open the occluded vessels

  • A common problem associated with Bare Metal Stents (BMS) implantation is instent restenosis, which occurs due to stent thrombosis, inflammation, and the proliferation and migration of Vascular Smooth Muscle Cell (VSMC) in the luminal area, which are collectively termed as neointimal hyperplasia (NH) [1,2,3]

  • The Fourier transform infrared (FTIR) spectrum of (Mg/Al) layered double hydroxide nanoparticles (LDH) is represented in Figure 1, which exhibits a broadband at 3451 cm−1 attributed to hydrogen bonding of the interlayer water with interlayer

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Summary

Introduction

The implantation of a balloon expandable stent by percutaneous coronary angioplasty is the most commonly used medical intervention to re-open the occluded vessels. A common problem associated with BMS implantation is instent restenosis, which occurs due to stent thrombosis, inflammation, and the proliferation and migration of Vascular Smooth Muscle Cell (VSMC) in the luminal area, which are collectively termed as neointimal hyperplasia (NH) [1,2,3]. Drug-eluting stents (DES) were developed in order to combat this problem, as the antiproliferative drug coated onto the stent prevents NH. Late stent thrombosis (ST) emerged with the use of DES due to the impaired re-endothelialization owing to the non-selectivity of anti-proliferative drug and polymer hypersensitivity [4,5]. The conventionally used anti-proliferative drugs, such as paclitaxel, sirolimus, rapamycin, and its derivatives, tend to impede endothelial cell (EC) proliferation in addition to VSMC due to induced autophagy [6]. The re-endothelialization of luminal stent surfaces is of utmost importance, because the functional and complete endothelial cell lining prevents the adhesion, aggregation, and activation of blood platelets and thereby inhibits late stent thrombosis [10]

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