Computational model of local intravascular drug delivery

Drug-eluting stents (DES) virtually eradicate the clinical phenomena of vessel restenosis; yet, they also increase the short and long term risks for stent thrombosis. To improve their safety and efficacy, it is critical to examine factors that alter local biologic outcome. The central hypothesis of this thesis is that local efficacy and toxicity are in part determined by the duration of drug exposure and local arterial drug concentrations. This thesis investigates how factors both intrinsic and extrinsic to the device impact local intravascular drug delivery. Computational models of local fluid mechanics and drug transport were formulated to study how arterial drug uptake is modulated by local blood flow, stent placement, administered drug dose and release kinetics, and the evolving local vascular response to the device. Lumenally flowing blood around stent struts was capable of transporting drug to the arterial wall in the presence of both single and multiple configurations of drug eluting stent struts. The extent of blood flow mediated arterial drug delivery depended upon the rate of drug release and administered dose. Slow drug release led to sustained, low magnitude drug uptake; exceedingly fast release resulted in transient and minimal tissue absorption due to rapid drug depletion.

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

• Balakrishnan, Brinda

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/1721.1/39570

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39570