[Fundamental study on hyperthermic chemotherapy using adriamycin-loaded hydroxyapatite].
We developed a porous hydroxyapatite ceramic (HAP) incorporating adriamycin (ADM), that is, ADM-HAP as a new delivery system (DDS) to release ADM gradually. We also researched the possibility of hyperthermic chemotherapy using ADM-HAP by in vitro and in vivo experiments. As for in vitro experiments, we implanted HAPs into uniform Agar-Phantom, and observed thermal distribution generated by Thermotron-RF 8 using thermography. Then we found the hot spot that the edge temperature of HAPs always at the range of 0.5-0.7 degrees C than in the other regions. On the other hand, slow constant release (1%) of ADM from ADM-HAP in PBS was recognized for 24 hrs up to 30 days. When the incubating temperature was shifted up to 42.5 degrees C or 44 degrees C from 37 degrees C, the quantity released over 24 hrs increased about 1.1-fold or 1.3-1.4-fold of the cases at 37 degrees C, respectively. In the in vivo experiment, we inoculated Sarcoma 180 cells in the leg of ddY-mice, and measured the tumor growing times by the treatment of hyperthermia+ADM (whole body), hyperthermia+ADM (tumor region) or hyperthermia+ADM-HAP (tumor region). Then we found that the effect of hyperthermia with ADM-HAP inhibited synergistically the tumor growth as compared with hyperthermia with ADM. Consequently, we succeeded in tumor growth inhibition by increasing the temperature and by limiting ADM release to only a target region using hyperthermia with ADM-HAP.
Nakatani
S
S
3rd Dept. of Internal Medicine, Kansai Medical University.
Kunieda
K
K
Seki
T
T
Wakabayashi
M
M
Inoue
K
K
Nagata
K
K
Murata
T
T
Tanaka
Y
Y
Sougawa
M
M
Kimura
R
R
D000818:Animals; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D017886:Durapatite; D006882:Hydroxyapatites / Q000008:administration & dosage*; D006979:Hyperthermia, Induced; D051379:Mice; D012513:Sarcoma, Experimental / Q000628:therapy*
D003692:Delayed-Action Preparations; D006882:Hydroxyapatites; D004317:Doxorubicin; D017886:Durapatite