Thermosensitive Liposomes for Image-Guided Drug Delivery

Abstract

Liposomes have been employed as cancer therapy clinically since the 1990s, with the primary benefit of reduced toxicity but no appreciable efficacy improvement. Thermosensitive liposomes (TSLs) are specifically formulated such that they release the encapsulated drug when exposed to hyperthermic temperatures in the fever range (~40-42°C) and have been investigated as cancer therapy for several decades, with first clinical trials initiated in the last decade. Combined with localized hyperthermia, TSLs allow precise drug delivery to a targeted region. Typically, the targeted tissue is exposed to localized hyperthermia facilitated by an image-guided hyperthermia device. Thus, TSLs enable image-guided drug delivery where drug is delivered to a tissue region identified by medical imaging. Recent TSL formulations are based on the more recent paradigm of intravascular triggered release, where drug is released rapidly (within seconds) while TSLs pass through the vasculature of the heated tissue region. The drug released within the blood then extravasates and is taken up by cancer cells. These TSLs enable up to 20-30 times higher tumor drug uptake compared to infusion of unencapsulated drug, and the dose locally delivered to the heated region can be modulated based on heating duration. This chapter reviews various TSL formulations, the different anticancer agents that have been encapsulated, as well as targeted cancer types. Further, the various hyperthermia devices that have been used for image-guided hyperthermia are reviewed, focusing on those that have been employed in human patients.

Keywords: Drug delivery; Drug targeting; Hyperthermia; Liposomes; Thermosensitive liposomes; Triggered release.