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

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.

Exploring Electrospun Scaffold Innovations in Cardiovascular Therapy: A Review of Electrospinning in Cardiovascular Disease

“…Studies in animal models have demonstrated that these stents may offer significant benefits over bare metal stents in the treatment of atherosclerosis. When investigating the effects of matrix elongation on the structure and drug release kinetics of polycaprolactone (PCL)-based electrospun paclitaxel (PTX)-enriched matrices, which are used as coatings for drug-eluting stents (DES), it was found that the arterial wall’s ability to retain and accumulate PTX results in prolonged drug release in rabbit models and could potentially allow for lower drug doses in the electrospun-produced coatings of stents [ 82 ]. A similar study on DES coated with an electrospun blend of polycaprolactone, human serum albumin, and paclitaxel found that they were less traumatic and induced less neointimal growth compared to bare metal stents in rabbit models [ 83 ].…”

Activated Carbon for Drug Delivery from Composite Biomaterials: The Effect of Grinding on Sirolimus Binding and Release

“…For example, previously, electrospun (ES) sirolimus (SRL) and paclitaxel-enriched matrices have been proposed for drug-eluting stent coating [ 14 , 15 ]. It was demonstrated that the artery wall effectively retains the drug released from the coating, and can reduce the required dose of the drug [ 16 ]. However, these stent coatings also release drugs into the blood, and the prevention of their release into circulation could be achieved by drug adsorption by an AC-enriched layer introduced into such coatings.…”