[Intraperitoneal administration of carboplatin loaded alpha-tricalcium phosphate (alpha-TCP) particles in rats bearing abdominal carcinomatosis].
It is difficult to treat abdominal carcinomatosis with conventional chemotherapy, and many kinds of localized chemotherapy have been attempted. We used alpha-tricalcium phosphate (alpha-TCP) particles as a drug carrier in this study. alpha-TCP, which has chemically similar properties to human bone, has an excellent biocompatibility with human tissues and is biodegradable. The particles measured 50 to 100 microns in diameter, were round in shape and very porous. These particles have many open micro-pores of about 1 to 3 microns, which are beneficial for containing drugs. The compatibility and biodegradation of alpha-TCP particles were studied following intraperitoneal (ip) administration in normal rats. The following results were obtained: (1) alpha-TCP particles were intaken in the great omentum, and dissolved gradually. (2) The efficacy of ip administration of carboplatin-loaded alpha-TCP (alpha-TCP-CBDCA) was examined using a Donryu rat model with AH130 abdominal carcinomatosis. The alpha-TCP-CBDCA contained 200 mg alpha-TCP and 4 mg CBDCA. The pharmacokinetics of CBDCA following ip administration of alpha-TCP-CBDCA were studied. Pt levels in ascites and great omentum were higher in the alpha-TCP-CBDCA ip from 0.5 to 168 hours than those in the free-CBDCA ip and iv groups. These results suggest that the efficacy of CBDCA may be enhanced by utilizing alpha-TCP particles as a drug delivery carrier.
Ueda
T
T
First Dept. of Surgery, Medical School, Nagoya City University.
Mizuno
I
I
Mohri
N
N
Akamo
Y
Y
Terada
J
J
Shibata
T
T
Yamamoto
T
T
Takeyama
H
H
Manabe
T
T
Yotsuyanagi
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001201:Ascites / Q000378:metabolism; D001673:Biodegradation, Environmental; D002130:Calcium Phosphates / Q000008:administration & dosage / Q000493:pharmacokinetics; D016190:Carboplatin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers; D007263:Infusions, Parenteral; D008297:Male; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010984:Platinum / Q000378:metabolism; D051381:Rats
D000970:Antineoplastic Agents; D002130:Calcium Phosphates; D004337:Drug Carriers; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D010984:Platinum; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; D016190:Carboplatin; C485829:calcium phosphate, dibasic, anhydrous