Poly(lactide-co-glycolide) Microspheres for Localized, Magnetic Resonance Imaging Monitored, Transcatheter Delivery of Sorafenib to Hepatocellular Carcinoma.

摘要

Hepatocellular carcinoma is the most common primary liver cancer and is the sixth most common cancer worldwide. Sorafenib has been proven efficacious against hepatocellular carcinoma (HCC) and is the standard of care for patients with advanced stage disease. However, oral systemic administration of sorafenib is associated with severe toxicities (hand foot syndrome, hypertension and gastrointestinal symptoms) and also reduces the dose of sorafenib that reaches the tumors. Typically, systemic administration of chemotherapeutics for HCC has been avoided through a procedure called transarterial chemoembolization (TACE), where a catheter is placed in tumor feeding arteries and a mixture of chemotherapeutics and embolic agents are delivered locally to the tumor. This works to contain the therapy locally at the tumor and to embolize the tumor feeding vessels to starve the tumor. Thus, in this thesis, we investigate the ability to re-formulate sorafenib as part of an embolic poly(lactide-co-glycolide) microsphere to enable local delivery of sorafenib as part of a TACE procedure. Additionally, we have incorporated iron oxide nanoparticles to enable MRI visualization of the microspheres for MRI monitoring of the delivery.