Vascular oligonucleotide transfer facilitated by a polymer-coated stent.

To evaluate the potential of clinically used phosphorylcholine (PC)-coated stents for their ability to load and release small decoy oligonucleotides (ODNs). Stents were loaded with 41 +/- 6 microg ODNs. Ex vivo deployment of ODN-loaded stents in explanted rabbit aortas showed significant vascular ODN transfer, with 18 +/- 12% of intimal or medial cell nuclei containing ODNs. In proof-of-principle in vivo experiments (using the double-injury rabbit model) there was no difference in fluorescent signal intensity between animals receiving ODNloaded stents or controls. However, a significant increase in signal intensity was detected in the kidneys of animals receiving ODN-loaded stents. PC-coated stents can be loaded with ODNs. Despite successful ex vivo ODN deposition and nuclear uptake in the vessel wall, in vivo vascular ODN transfer was not achieved. Rapid intravascular release of ODN before implantation and potential vascular barriers for gene transfer are most likely responsible for the currently unsatisfactory in vivo release kinetics.

Biological evaluation and drug delivery application of cationically modified phospholipid polymers.

Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased. Platelet activation assays, measurement of plasma coagulation time and whole blood contact scanning electron micrography demonstrated that the haemocompatibility of the coatings was shown to be unaffected by the CMA component. The CMA polymer coatings have been shown to absorb/adsorb many different drug compounds covering a wide range of molecular weights and release these in a controlled fashion. The range of cationic polymers assessed can interact with the net negative charge found in many large therapeutic biomolecules, such as DNA fragments used in gene therapy, that may be of interest in the preventative treatment of conditions such as restenosis. Coronary stents coated with 6% or 20% CMA-containing polymers have been shown to load and release this type of genetic material irrespective of molecular weight of the biomolecule. Ex vivo and in vivo studies have shown that these compounds can be delivered to the stented section of the vessel with very low quantities delivered outside the vessel target area.

Angiopeptin-eluting stents: observations in human vessels and pig coronary arteries.

Local drug delivery from polymer-coated coronary stents may reduce the incidence of in-stent restenosis. Angiopeptin, an inhibitor of smooth muscle cell proliferation, may reduce the clinical impact of restenosis. The objectives of this study were to characterize the release kinetics and distribution of angiopeptin-loaded phosphorylcholine (PC)-coated drug delivery (DD) BiodivYsio stents and assess their safety and efficacy at reducing neointima formation. I125-angiopeptin-loaded DD-PC-coated stents were implanted into human saphenous vein segments ex vivo, and I125 angiopeptin was detected in the medial layer at 1 hour. When implanted in pig coronary arteries, I125 angiopeptin was found adjacent to the stent at intervals up to 28 days. No significant amounts were found elsewhere. To assess efficacy, twelve angiopeptin-loaded DD-PC-coated stents, twelve non-loaded DD-PC stents, ten standard PC-coated stents and 8 uncoated stents were implanted into normal porcine coronary arteries. Stents were harvested at 28 days and neointima formation was assessed by computerized morphometry. No adverse tissue reactions were seen with any of the PC-coated stents. No significant differences were seen in neointimal or luminal cross-sectional areas between study groups. Local delivery of I125 angiopeptin into the vascular wall can be achieved using a PC-coated stent. Delivery of angiopeptin from drug delivery PC-coated stents is safe, but does not lead to a significant reduction in neointimal growth at 28 days within the parameters of this study.