Design and Analysis of an Acoustically-Active Paclitaxel Nanocapsule-Bound Microbubble Vehicle for Ultrasound-Targeted Chemotherapy

 

Trainee:

Lee Mullin

mullin

Research Mentor:

Dr. Paul Dayton, PhD

dayton

Clinical Co-mentor:

Dr. Julian Rosenman, MD

rosenman
Home Department Biomedical Engineering
Project Description

The development of a drug vehicle that could target a tumor or organ with high specificity and improve therapeutic efficacy, while reducing side effects, is of particular interest for chemotherapy administration. Combining ultrasound technology with nanoparticle drug capabilities is a promising method of achieving targeted drug delivery. In chemotherapy, nanoparticles offer a promising alternative to conventional methods due to their size and high payload. We propose that by combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, we can overcome nonspecificity of current chemotherapy delivery techniques.

Ultrasound microbubble contrast agents are lipid-encapsulated gaseous microspheres that improve the quality of ultrasound images due to the difference in acoustic impedance between their gaseous core and the surrounding medium. Because they are acoustically active, microbubbles are an appealing choice for drug delivery. Using acoustic radiation force, the microbubbles can be localized and concentrated at a target site, such as a tumor. Along with controlling the movement of microbubbles, ultrasound is also capable of increasing cellular and vascular permeability. This effect is enhanced with the addition of ultrasound contrast agents due to cavitation of the bubbles and microjet/streaming that occurs when the microbubbles are exposed to high-energy pulses. Additionally, ultrasound pulses can destroy microbubbles thereby depositing material at desired locations. Combining acoustic radiation force and microbubble destruction has the potential to greatly increase drug delivery at the targeted location.

The goals of my research will be to examine the ability of ultrasound to enhance local nanoparticle drug delivery in-vitro and evaluate the efficacy of ultrasound enhanced therapeutic delivery in-vivo through noninvasive ultrasound imaging and pharmacokinetic methods.