CHAPTER 2:Materials Science and Engineering of the Low Temperature Sensitive Liposome (LTSL): Composition-Structure-Property Relationships That Underlie its Design and Performance

This chapter presents the material science and materials engineering concepts that went into the design and testing of the Low Temperature-Sensitive Liposome (LTSL), including: the roles of each of the components that make up the composite membrane; how the molecular and nanostructures that they form might influence the already anomalous permeability at the phase transition of the bilayer; and how this thermally sensitive “Smart Drug Delivery System” leads to ultrafast release of a loaded doxorubicin drug, triggered and controlled in the micro-vasculature of tumors by applied mild hyperthermia. This formulation approach, as ThermoDox®, has been used in a completed 700-patient Phase III human clinical trial in liver cancer (HEAT study), is in a Phase II trial in chest wall recurrence of cancer (DIGNITY study) and has been used in a Phase I trial of patients with colorectal liver metastases (ABLATE study). With additional research and preclinical studies underway, and a range of other drugs, imaging agents and biological modifiers poised for encapsulation, the LTSL could provide a new paradigm for drug and agent delivery for the treatment of localized tumors: rapid triggered drug release in the tumor bloodstream and deep penetration of drug into the tumor tissue.