Global gene expression analysis of the effects of Vinblastine on endothelial cells, when eluted from a thermo-responsive polymer

Abstract

In-stent restenosis remains a significant problem associated with bare metal stents. This drawback has prompted research into improving stent design and the development of novel coatings, including drug-eluting stents. A number of drug-eluting stents are currently on the market; however, the success rate of these stents in complex situations has been found to be quite low. Thus, there remains potential for the development of more suitable drug-eluting stents. The aims of this study were to use a thermoresponsive polymer to develop a system to locally deliver vinblastine, an antimitotic agent currently used as an anticancer drug, and in addition, assess the effects of this drug at the gene expression level in vitro. An N-isopropylacrylamide/N-tert-butylacrylamide (NiPAAm/NtBAAm) copolymer solution in the ratio 65:35 was prepared and appropriate volumes of vinblastine were added to generate two final drug concentrations of 22 nanomoles/film or 0.022 nanomoles/film. Stainless steel discs (316) were coated with the copolymer solution or this solution containing drug. Human endothelial cells were cultured on collagen type 1 gels and then incubated with the coated discs for 24 h. Gene expression studies using oligonucleotide microarray analysis and quantitative RT-PCR were then performed. Microarray analysis revealed that vinblastine causes the differential expression of a range of genes involved in a variety of different functions, including cell cycle and apoptosis. The changes in expression of some of these genes culminate in cell cycle arrest and apoptotic pathways. (c) 2006 Wiley Periodicals, Inc.