Magnetic microbubbles: investigation and design of new formulations for targeted therapy

Thesis

Targeted therapy is a significant area of research in pharmaceutical and biomedical science. Its overall aim is to achieve maximum impact on malignant cells with minimum side effects to healthy tissue. In this thesis the capabilities of magnetic microbubbles as targeted therapeutic delivery vehicles are explored. New characterisation techniques were developed in order to understand and improve the current magnetic microbubble formulation. Electron microscopy was used to analyse the nanoscale structure of microbubble shells and observe nanoparticles attached to the shell surface. A new flow phantom was developed and the targeting of magnetic microbubbles against flow conditions corresponding to those in the human body was found to be feasible in numerous vessel sizes and flow conditions. Magnetic targeting of microbubbles was also observed in a perfused porcine liver model. Magnetic targeting was then attempted against flowing blood and a decrease in targeting efficiency observed. This was also seen for biochemical targeting and collisions with red blood cells identified as the most likely cause. Importantly, the number of magnetically targeted microbubbles significantly exceeded those targeted via biochemical interactions in both blood and water. In the second part of the thesis new types of magnetic microbubble were developed. The first exploits the fusion of nano-scale magnetic droplets with phospholipid microbubbles. In the second magnetic nanoparticles were incorporated directly into the lipid shell. The new magnetic microbubble formulation could be magnetically targeted, observed via contrast ultrasound and was successfully used to deliver siRNA to neuroblastoma cells.

Authors: Owen, J; Joshua Owen

• Publication date: 2014
• DOI: 10.5287/ora-eyogrodbb
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: Ultrasound; Microbubbles; Magnetism; Drug delivery
• Subjects: Biomedical engineering