Survival of Endothelial Cells in vitro on Paclitaxel-loaded Coronary Stents

Abstract

Coronary stents that are developed for use with balloon angioplasty are known to cause acute occlusion and long-term stenosis. It is likely that a controlled release of drugs at the site of stent implantation might inhibit the proliferation of vascular smooth muscle cells (VSMC) and reduce restenosis. However, if the drug is necrotic and affects cell survival near the implant, it may interrupt the local tissue regeneration. Different methods have been used for the immobilization of drugs with stents to get an effective concentration that inhibits cell proliferation. The objective of this study is to assess the effectiveness of Paclitaxel-loaded stents by immobilization with a biodegradable polymer, to inhibit cell proliferation. The cells used for the evaluation are human umbilical vein endothelial cells (HUVEC) and the proliferation rate of these cells on the drug-coated stent is compared against an uncoated stent for a 72-h period. Evaluations were also made to differentiate between cell apoptosis and necrosis to prove that the drug released is not deleterious to the surrounding tissue. While a similar initial cell adhesion is observed in bare and coated stents, the proliferation of HUVEC is negligible when grown on a drug-coated stent (p < 0.001). By specific staining techniques, the cells on the drug-coated stents are found to be apoptotic and not necrotic, throughout the evaluation period. In vitro leukocyte adhesion and platelet deposition on the drug-coated stents are found to be low when they are exposed to human blood and platelet-rich plasma (PRP), suggesting that the coated stents may not be thrombogenic in vivo. Therefore, drug coating of stents using the described technique may have a considerable promise for the prevention of neointimal proliferation, restenosis, and associated failure of angioplasty.

Eluting characteristics of a platelet glycoprotein receptor antibody using a PLLA-coated stent

“…This study confirms earlier results from Prasad et al [44,45] advocating the need of multiple layers of coatings to optimize the in vitro and in vivo results obtained with paclitaxel. Basically, the stents were sandwiched in 3 layers of coating, with only the two layers closest to the metallic frame containing elutable drugs.…”

Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

“…They also confirmed that in an appropriate concentration range, paclitaxel did not cause necrosis of the surrounding tissue and did not affect the healing and epithelialization of the tracheal mucosa. [2526]…”

Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells

“…21 Others have shown that apoptosis is induced in human umbilical vein endothelial cells grown for 72 hours on paclitaxel eluting stents. 36 However, minimal induction of apoptosis was observed by paclitaxel. TNF-a did not enhance apoptosis nor did it interact with paclitaxel.…”