The development of particle-coated stents and balloons
Abstract
Atherosclerosis results from an accumulation of fatty plaque in blood vessels which causes a blockage of blood circulation. Balloon angioplasty and bare metal stents are used to restore the diameter of an occluded artery, but the restenosis rate is still high owing to neointimal hyperplasia. A drug-eluting stent (DES) carrying anti-proliferative agent has been developed to overcome restenosis in an atherosclerotic artery. Nevertheless, DESs create other issues, such as prolonged inflammation, endothelial dysfunction, and late stent thrombosis. Durable polymers used in the first and second generations DESs are suspected to stimulate a hypersensitivity reaction and prolong inflammation. Moreover, anti-proliferative drugs released from DESs do not have specificity only on vascular smooth muscle cells, but also they retard the re-endothelialization which is required for stent coverage and anti-thrombogenic surface of arterial walls. There are some strategies to overcome these drawbacks, including using a combination of anti-proliferative drug and prohealing drug on a DES, and using no polymer or biodegradable polymer for coating. A single or a combination of these approaches has been tried in the recent DES development. The newest concept is a drug-eluting balloon (DEB) which is able to deliver the drug quickly, yet effectively, to the vascular wall without leaving persistent polymer or drug. In this study, the formulations and the methods for a coating of DESs and DEBs were established. Paclitaxel and estradiol were formulated and coated by layer-by-layer technique to provide 2 different release kinetics and this dual-release DES was examined for potential problems for the polymeric coating. Next, the soft lithography using hydrogel templates was applied to fabricate polymeric and drug particles used for coating DESs and DEBs in this study. Drug particles were loaded on the metal stent surface based on the idea that the solubility of a drug varies in different solvents. Finally, 4 different methods to load polymeric particles on the balloon's surface were proposed, and the release of particles from the coated balloon was investigated.
Degree
Ph.D.
Advisors
Park, Purdue University.
Subject Area
Pharmacy sciences
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