DOI
https://doi.org/10.25772/VQEK-7W66
Defense Date
2011
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Chemistry
First Advisor
Everett Dr. Carpenter
Abstract
The main challenge in disease treatment is no more the discovery of new therapeutic drugs, but to provide targeted delivery of therapeutic drugs to specific sites without incurring systemic toxicity effects. An efficient way of reducing the toxicity is by encapsulating the drug with a biodegradable matrix that can provide controlled release of the drug along with local heating of the drug. Local heating can be obtained by incorporating magnetic iron oxide particles that heat upon exposure to AC electromagnetic fields. The magnetic iron oxide nanoparticles are also gaining much attention as MRI contrast agents. Thus it would be of potential benefit if a drug delivery system is designed to encapsulate the drug as well as the magnetic iron oxide nanoparticles within a biodegradable matrix, thereby providing a dual modal imaging and therapeutic delivery system. The key step in the design of a dual modal drug delivery system is the encapsulation of the magnetic iron oxide nanoparticles with polymer of choice. The magnetic iron oxide nanoparticles were encapsulated into a robust poly (styrene-co-vinylbenzylchloride-co-divinylbenzene) (PSVBDVB) to study these synthetic variations upon encapsulation with a polymer. The next step to the design of drug delivery system was to replace the PSVBDVB polymer by a biocompatible and biodegradable polymer- Poly (lactide-co-glycolide) (PLGA). The PLGA composites containing the Fe@FeOx core shell nanoparticles and the drug analog [Ru(bpy) dye] was prepared by oil-in water emulsion solvent evaporation technique. The local heating of the PLGA composites was also achieved by irradiating the Fe@FeOx nanoparticles with 2.45 GHz microwave radiations. Higher Ru(bpy) dye release from the composites by locally heating the sample with 2.45 GHz microwave pulse compared to externally heating the composite sample was achieved. The final step was the design of controlled release drug delivery system with dual modal imaging and therapeutic capabilities. To obtain narrow sized PLGA composites the Fe@FeOx nanoparticles were replaced by chloroform based ferrofluid. The ferrofluid was synthesized by novel thermolysis technique. The release of the dye from the PLGA composites when placed in the Rf induction coil was determined by fluorescence spectroscopy and a linear increase in the fluorescent intensity was observed with time. Also, the controlled release of the dye from the composites was achieved by a pulsed Rf treatment. Magnetic resonance imaging was also performed using the PLGA composites which showed enhancement in the T2-weighted image contrast and thus negligible reduction in the contrast capabilities of the iron oxide particles (R2 = 58.7 s-1mM-1). The PLGA composites containing the drug analog and the iron oxide nanoparticles thus constitute a controlled release drug delivery system with dual modal imaging and therapeutic capabilities.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
December 2011