Improvements in Ultrasound Mediated Drug Delivery using Microbubble Contrast Agents and Application in Ex-Vivo Porcine Eyes

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Feingold, Steven
- Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering

Abstract

Ultrasound mediated drug delivery is a growing field which shows great promise. However, the ability to uniformly deliver acoustic energy to large 3D volumes of tissue remains a challenge for drug delivery. Additionally, uneven drug loading and large size distributions in microbubble contrast agents (MCAs) reduce the ability to control therapeutic dosing. The aim of this thesis is to demonstrate improvements in the field through new techniques in producing acoustically active drug delivery agents and applying ultrasonic parameters to volumetric regions of interest. The use of a computer controlled motion stage to apply ultrasound to a 3D volume of tissue is shown, allowing the uniform delivery of destructive pulses and acoustic radiation force. This technique is demonstrated in a novel application for treating diseases of the posterior segment of the eye. Injections of MCAs loaded with fluorescent dye into the suprachoroidal space of ex-vivo porcine globes are used to assess the feasibility of ultrasound mediated drug delivery for treating tissues in the rear of the eye. Also demonstrated is the production of MCAs with a controlled size and drug loading distribution for oil soluble compounds, which could enable greater control over therapeutic dosing.

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