Implantation treatment method of slow release anticancer doxorubicin containing hydroxyapatite (DOX-HAP) complex. A basic study of a new treatment for hepatic cancer.
We performed an experimental study on slow releasing anticancer drug implantation treatment as a new therapy for hepatocellular carcinoma. Hydroxyapatite (HAP) was chosen for the carrier material and doxorubicin hydrochloride (DOX) for anticancer agent. DOX-HAP was produced by adsorbing DOX to porous HAP particles of 1375 +/- 125 microns diameter using the freeze drying method. In vitro experiments showed slow release of the drug resulting in the steady release of DOX from HAP for 1 month duration. In healthy white rabbits with DOX-HAP implantation in the liver, serum DOX was not detectable, and DOX release rate was stable at the implanted region after 7, 14, and 21 days. When DOX-HAP (DOX; 100 mg kg-1) was administered to mice with sarcoma 180, an improved survival rate was observed without acute toxicity. We also found that VX2 liver tumour growth on white rabbit was inhibited by implantation of DOX-HAP, without acute toxicity. We hope that DOX-HAP implantation therapy will open up new avenues for the treatment of hepatoma.
Kunieda
K
K
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Seki
T
T
Nakatani
S
S
Wakabayashi
M
M
Shiro
T
T
Inoue
K
K
Sougawa
M
M
Kimura
R
R
Harada
K
K
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers; D004343:Drug Implants; D006882:Hydroxyapatites / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011817:Rabbits; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D006882:Hydroxyapatites; D004317:Doxorubicin