Drug deposition and distribution in healthy and atherosclerotic arteries and in models of atherosclerosis following bulk or stent-based drug delivery

Drug eluting stents have revolutionized the practice of medicine and the landscape of medical devices. Yet, more than four years after introduction clinical trial data and clinical use have still not fully clarified what drives the safety and efficacy of these devices. The goal of this thesis was to help fill this void by describing the mechanisms by which stent-eluted drugs are distributed within healthy and atherosclerotic vascular models. In the first part of the thesis we investigated the effect of drug physicochemical properties on drug deposition, retention, and distribution in a healthy vascular model. We found that hydrophobic drugs are deposited to a far greater degree than hydrophilic drugs, with longer retention times, and distribution patterns that likely track with specific and general binding sites. The second part of the thesis investigated how arterial ultrastructure in health and disease modulates the arterial deposition and distribution of hydrophobic antiproliferative drugs used with drug-eluting stents. We tracked the distribution of radiolabeled and FITC-labeled compounds and demonstrated that macrostructural changes in arterial architecture led to profound changes in drug deposition. Paclitaxel in particular was sensitive to tissue state.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Vukmirovic, Neda

Advisor dc:contributor.advisor

• Elazer R. Edelman.

• Harvard University--MIT Division of Health Sciences and Technology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/40871

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/40871