Hyperthermia enhancement by thermosensitive liposome as a drug delivery system for malignant glioma chemotherapy

Abstract

We described herein the effectiveness of hyperthermia as a promising drug delivery system, especially noticing malignant glioma thermo-chemotherapy. Previously the authors reported that the combination of thermosensitive liposome containing CDDP and localized hyperthermia using a radiofrequency antenna focused CDDP to the experimental brain tumor, providing a greater antitumor effect. Our hyperthermic treatment, above 42°C, can treat the entire tumor core of human malignant glioma for direct thermal killing. When heating, the 40°C area extended up to a wide portion, covering the area invaded by tumor cells. Therefore, a more effective thermosensitive liposome was developed for clinical use. It was designed to release adriamycin (ADR) at 40°C and above. As a result, this new thermosensitive liposome sharply released ADR at a temperature of 40°C as planned, bringing a significantly greater antitumor effect in rat tumor models. This procedure will 1) contribute to the synergistic effect of hyperthermia and antitumor drugs in regions heated above 42°C, 2) be effective in direct thermal killing, 3) help to deliver the antitumor drugs wider : to the tumor core, and also to the area invaded by tumor cells, both areas heated at 40°C and above, 4) permit application of ADR and other antitumor drugs regardless the blood-brain barrier problem. Our present hyperthermic treatment can be easily applied to the elder, and/or ill patients, even those with deep seated glioma. Taking all these advantages into consideration, we can suggest the wider effects achieved by the use of this drug delivery system.