Therapeutic efficacy of targeting chemotherapy using local hyperthermia and thermosensitive liposome: evaluation of drug distribution in a rat glioma model.
A method was developed of targeting chemotherapy using thermosensitive liposomes to treat malignant gliomas. Using the brain heating system, when the tumour core is heated to >43 degrees C, the tumour infiltrating zone is exposed to mild hyperthermia (40-43 degrees C). Thermosensitive liposomes were designed to release their contents at 40 degrees C to target both the tumour core and tumour infiltrating zone. The present study investigated the anti-tumour effect on rat glioma models in tumour drug uptake and tumour growth delay studies. Elevated accumulation of ADR in the rat C6 glioma after treatment was obtained in the area heated to >40 degrees C. However, there was no significant difference between the areas heated to 40-42 degrees C and >43 degrees C. Furthermore, it was found that ADR concentrations in the mildly hyperthermic areas were significantly higher following treatment with liposomal ADR than with free ADR. The animals treated with the new combination therapy had significantly longer overall survival time in comparison to those receiving other treatments. Thus, thermosensitive liposomes release their contents in response to mild hyperthermia and this combination therapy has a greater therapeutic efficacy for malignant brain tumours. This method is a promising approach for the treatment of malignant glioma patients.
Aoki
H
H
Department of Neurosurgery, Brain Research Institute, Niigata University, Asahimachi 1, Niigata 951, Japan. aoki@nice-hp.or.jp
Kakinuma
K
K
Morita
K
K
Kato
M
M
Uzuka
T
T
Igor
G
G
Takahashi
H
H
Tanaka
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D007036:Hypothermia, Induced / Q000295:instrumentation / Q000379:methods*; D008081:Liposomes / Q000627:therapeutic use*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D015996:Survival Rate; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin