Vascular Stents Coated with Electrospun Drug-Eluting Material: Functioning in Rabbit Iliac Artery

Abstract

A stenting procedure aimed at blood flow restoration in stenosed arteries significantly improves the efficiency of vascular surgery. However, the current challenge is to prevent neointimal growth, which reduces the vessel lumen, in the stented segments in the long run. We tested in vivo drug-eluting coating applied by electrospinning to metal vascular stents to inhibit the overgrowth of neointimal cells via both the drug release and mechanical support of the vascular wall. The blend of polycaprolactone with human serum albumin and paclitaxel was used for stent coating by electrospinning. The drug-eluting stents (DESs) were placed using a balloon catheter to the rabbit common iliac artery for 1, 3, and 6 months. The blood flow rate was ultrasonically determined in vivo. After explantation, the stented arterial segment was visually and histologically examined. Any undesirable biological responses (rejection or hemodynamically significant stenosis) were unobservable in the experimental groups. DESs were less traumatic and induced weaker neointimal growth; over six months, the blood flow increased by 37% versus bare-metal stents, where it increased by at least double the rate. Thus, electrospun-coated DESs demonstrate considerable advantages over the bare-metal variants.

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

“…The data on PTX delay in the arterial wall when incubated under conditions similar to those in vivo [ 2 ] are in favor of the long-term maintenance of the sub-cytotoxic drug concentration in the arterial wall and make it possible to reduce the dose of drugs introduced into the coating.…”

“…ES solutions were prepared as described in Section 2.2 . A polished stainless-steel rod (1.0 mm in diameter and 30 mm in length) with a previously installed metal stent (min/max diameter 2.0/3.5 mm; Angioline, Novosibirsk, Russia) was used as an electrode [ 2 ]. A coating of 125–150 µm was applied onto the stent under the conditions described in Section 2.2 .…”

“…Recently 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 ].…”

“…Two ES products (esophageal stent and heart valve prostheses) were granted to FDA-approved clinical studies [ 19 ]. The advantages of coating stents with electrospun-produced matrices are the following: (1) drug release can be controlled through the structure of polymer fibers; (2) the drug is equally distributed across the surface of the entire stented section of the artery; (3) the coating distributes the load of the strut-wall contact region to the entire surface area occupied by the stent; (4) like an endothelial coating, it performs a barrier function, preventing tissue debris from entering into the blood, as well as eliminating direct contact between blood cells and the damaged tissue [ 2 ].…”

“…These matrices do not exert additional stress on the stent beams, they exhibit two-phase PTX release kinetics providing a prolonged PTX release, and they can potentially maintain a therapeutic PTX concentration in the arterial wall. The stents coated with 5%PCL/10%HSA/3%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 ]. Manipulations performed during the stent installation can affect the integrity and properties of the stent’s coatings.…”