Influence of Elongation of Paclitaxel-Eluting Electrospun-Produced Stent Coating on Paclitaxel Release and Transport through the Arterial Wall after Stenting.

Zhanna K Nazarkina,Boris P Chelobanov,Konstantin A Kuznetsov,Pavel P Laktionov,Andrey A Karpenko,Alexey V Shutov,Irina V Romanova

doi:10.3390/polym13071165

Abstract

It was previously shown that polycaprolactone (PCL)-based electrospun-produced paclitaxel (PTX)-enriched matrices exhibit long-term drug release kinetics and can be used as coatings for drug-eluting stents (DES). The installation of vascular stents involves a twofold increase in stent diameter and, therefore, an elongation of the matrices covering the stents, as well as the arterial wall in a stented area. We studied the influence of matrix elongation on its structure and PTX release using three different electrospun-produced matrices. The data obtained demonstrate that matrix elongation during stent installation does not lead to fiber breaks and does not interfere with the kinetics of PTX release. To study PTX diffusion through the expanded artery wall, stents coated with 5%PCL/10%HSA/3%DMSO/PTX and containing tritium-labeled PTX were installed into the freshly obtained iliac artery of a rabbit. The PTX passing through the artery wall was quantified using a scintillator β-counter. The artery retained the PTX and decreased its release from the coating. The retention of PTX by the arterial wall was more efficient when incubated in blood plasma in comparison with PBS. The retention/accumulation of PTX by the arterial wall provides a prolonged drug release and allows for the reduction in the dose of the drugs in electrospun-produced stent coatings.

Highlights

We have shown that electrospun (ES)-produced paclitaxel (PTX)-enriched matrices are suitable for vascular stents coating ) [1,2]
The stents coated with 5%PCL/10%human serum albumin (HSA)/3%dimethyl sulfoxide (DMSO)/PTX demonstrated a weaker neointima growth, a slower increase in the blood flow rate, and the absence of arterial wall thickness in comparison with bare-metal stents after in vivo installation in a rabbit iliac artery [2]
Matrices produced from 5%PCL/10%HSA/3%DMSO/PTX are most suitable for stent coatings, exhibiting long-term PTX release kinetics [1]

Summary

Introduction

We have shown that electrospun (ES)-produced paclitaxel (PTX)-enriched matrices are suitable for vascular stents coating ) [1,2]. Drug-eluting stents (DES) were designed to minimize neointima growth after angioplasty [3]. PTX is one of the most commonly used drugs for in-clinic peripheral DES coatings. PTX was shown to inhibit smooth muscle cell (SMC) proliferation and migration and prevent neointima formation after angioplasty [5]. According to Kuno et al, PTX-eluting stents and balloons did not increase short-term mortality vs balloon angioplasty [7]. PTX-eluting stents did not show a significant increase in long-term mortality vs balloon angioplasty. PTX-coated balloons showed a significant increase in long-term mortality compared to balloon angioplasty and bypass. In contradistinction to PTX-coated balloons that deliver a large drug dose over a short time period, stents with lower drug doses provide prolonged

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