Mild Hyperthermia and Thermosensitive Liposomes for Chemotherapy

Liposomes are nano-sized drug carriers widely used to deliver chemotherapeutic compounds in cancer treatments. While prolonging drug retention in circulation and preventing certain toxic side-effects, liposomal drugs still need to overcome matters on specific accumulation in the tumor and controlled drug release. The aim of this thesis is to introduce local mild hyperthermia (HT) and thermosensitive liposomes (TSL) to liposomal chemotherapy, to improve therapeutic outcome. At present, two major drug delivery approaches using TSL and mild HT are being proposed. The first approach aims to use mild HT in a two-step approach to first manipulate tumor vasculature, promoting enhanced liposome extravasation, followed by a second mild HT to trigger drug release. A second drug delivery approach is the intravascular drug release approach in which circulating TSL are triggered to rapidly release their contents upon their passage through tumor vasculature. The two-step mild HT approach was less effective compared to intravascular release approach. However, the two-step mild HT approach is an alternative to conventional mild HT, and may be more beneficial to large and deep seated tumors when regional mild HT is required. Our TSL formulation, with an optimized poly(ethylene glycol) (PEG) surface concentration for stability at physiological temperature and fast release at mild HT (41-43°C), further prolonged tumor growth control and improved survival than lyso-lipid based TSL when applied in combination with mild HT.

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