Preclinical evaluation of paramagnetic temperature sensitive liposomes for image-guided drug delivery

Kneepkens, Esther (cover) web

Thesis Muijlwijk, K.

Eindhoven University of technology

This thesis describes the preclinical development of image-guided drug delivery from temperature-sensitive liposomes (TSLs) induced by magnetic resonance guided high intensity focused ultrasound (MR-HIFU). Traditional chemotherapy of solid tumors is complicated by a narrow therapeutic window. Encapsulation of the drug inside a TSL enables heat-triggered local drug delivery to tumors, while minimizing systemic exposure and associated side effects. Non-invasive tumor heating is accomplished by focusing high intensity ultrasound waves inside the tumor. Depending on the clinical need, the tumor can be heated to ablative (>450C) or hyperthermic (40-440C) temperatures to either cause direct heat-inflicted cell death, to deliver TSL-encapsulated chemotherapeutics or both. In this process, MRI guidance is crucial; it is ised to delineate the treatment area and it offers temperature feedback throughout the HIFU treatment. Additionally, by encapsulation of a MR contract agent, drug release from TSLs can be monitored throughout the treatment, giving insight in both the spatial distribution of the drug and an estimate of the delivered drug concentration.