Defining Delivery Pathways of Nanoparticles

The goal of nanomedicine is to use nanoparticles to carry drugs to specific target site in the body. For cancer nanomedicine, a recent meta-analysis showed that only 0.7% of the injected nanoparticles reach the tumour. To address this delivery inefficiency, it is important to examine each biological barrier to determine its impact on delivery. In this thesis, first the body was modelled as a series of barriers that nanoparticles need to overcome successively in order to access the target site. The model shows that the number and strength of barriers limits what is available to be delivered. The macrophages of the liver can sequester up to 99% of the injected nanoparticles, and thus are the biggest barrier for targeted delivery. Next, clodronate-liposomes were used to remove the liver macrophages and showed that both nanoparticle tumour delivery and hepatobiliary elimination can be improved. Specifically, nanoparticle tumour delivery can be increased up to 50× and hepatobiliary elimination up to 10×. Removal of the liver macrophages then allowed the exploration of other secondary barriers to delivery such as tumour pathophysiology and the liver sinusoidal endothelium. Together, these studies define concepts and strategies that can improve nanoparticle delivery and reduce unwanted bioaccumulation to pave the way for their clinical translation and regulatory approval.

Department dc:contributor.department

Biomedical Engineering

Year dc:date.issued

2020

Author dc:creator

• Poon, Wilson

Advisor dc:contributor.advisor

• Chan, Warren CW

• Cancer
• Drug delivery
• Elimination
• Kupffer Cells
• Liver
• Nanoparticles

Handle dc:identifier.uri

http://hdl.handle.net/1807/106122

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/106122