"Thermosensitive Liposomes: A Therapeutic Strategy to Enhance the Effectiveness of Nanomedicines in Oncology"
Dr. Christine Allen (University of Toronto)

Liposomes are one of the few drug delivery platforms that have resulted in clinically approved products in oncology. Notwithstanding this success, the approved liposome formulations largely result in improvements in the toxicity profile of drug with limited to no enhancements in efficacy.  In addition, a number of drugs relying on formulation in liposomes have failed in clinical development.  The many pre-clinical and clinical studies that have been conducted on liposomes have revealed a number of limitations associated with this technology.  These include variability in tumor accumulation due to clinical heterogeneity in the enhanced permeability and retention (EPR) effect as well as poor tumor penetration, and in some cases, limited drug release once at the tumor site.  Thermosensitive liposomes have the potential to address these issues, in particular, when they are designed to provide largely intravascular release of drug within the tumor region. 

Our laboratory has designed a thermosensitive liposome formulation of cisplatin that provides triggered drug release in response to temperatures in the mild hyperthermia range.  This presentation will review our data obtained to date with this formulation in combination with mild hyperthermia in a series of tumor xenograft models of human cervical, lung and breast cancers.  The factors that impact the effect of this therapeutic strategy will be discussed including tumor microenvironment parameters such as microvessel density, degree of hypoxia, stromal content, cell sensitivity to drug and heat shock protein expression.

Dr. Allen is Professor and the GlaxoSmithKline Chair in Pharmaceutics and Drug Delivery in the Leslie Dan Faculty of Pharmacy at the University of Toronto. She is the guest of Prof. John Oh