Date of Award

1-1-2010

Document Type

Campus Access Dissertation

Department

Chemical Engineering

First Advisor

James A Ritter

Abstract

The lack of drug selectivity to a specific site has been one of the major limitations in current therapeutic treatments. To overcome these limitations, many approaches have been proposed, one of which is magnetic drug targeting (MDT). The concept of MDT is to use drug carriers that contain a magnetic component and guide these carriers to a specific site with the aid of an external magnetic source. These magnetic drug carrier particles (MDCP) can be used to deliver a drug to the desired site and increase the amount of treatment locally in the diseased tissue, subsequently reducing adverse side effects to healthy tissue and the required amount of pharmacological agents. Limitations in the traditional MDT approach, i.e. dynamic forces overcome magnetic forces, have led researchers to study the use of implants to increase magnetic forces and the collection of MDCPs. This method is termed implant assisted (IA) - MDT, which exploits basic principles of high gradient magnetic separation to improve local drug retention.

The work herein will address the design and use of novel methods to improve the collection of MDCPs using IA-MDT. Ferromagnetic nanoparticles, wire filaments and stents were used in vitro as possible implants, showing that in their presence an increase of more than 15% collection of MDCPs was obtained, as opposed to the traditional MDT scenario. Biodegradable magnetic nanocomposite stents were also fabricated and proved to be a successful magnetic implant with comparable results to their metallic counterparts and the benefit of degrading naturally, thus preventing physiological complications, i.e. restenosis. Organ perfusion experiments were also carried out on swine heart tissue with stent implants in the right coronary artery. The results from this work with animal tissue under physiological conditions showed similar trends to previous theoretical studies and an increase of more than 30% of MDCPs collection in some cases, compared to controls in the absence of the magnetic field and the traditional MDT setup.

Rights

© 2010, Jan O. Mangual

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