A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of particle size and dose on chitin-containing cis-diamminedichloroplatinum(II) albumin microsphere antitumor activity in VX2 hepatic tumor model rabbits.
We prepared chitin-containing cis-diamminedichloroplatinum(II) (CDDP) albumin microspheres with various particle sizes, and investigated in vitro CDDP release; the antitumor effect towards VX2 tumor introduced into rabbits was then examined. It was found that the rate of release of CDDP from chitin-containing CDDP albumin microspheres in vitro was increased with reduced particle size. Administration of microspheres to VX2 tumor-bearing rabbits via the hepatic artery resulted in different profiles of plasma platinum concentration depending on the particle size, and a higher concentration of platinum was released from the beginning of administration as particle size was reduced. The platinum content in hepatic tissue following the administration of CDDP microspheres was increased as the particle size decreased, although the rate of increase was not uniform. The antitumor effect of CDDP assessed by the suppression of tumor growth tended to be higher when microspheres of smaller sizes were used. However, no significant difference was observed in tumor growth rate between rabbits injected with microspheres smaller than 20 microns and those injected with sizes between 20 and 37 microns (p > 0.05). We also examined the relationship between the CDDP dose and antitumor effect using microspheres of less than 20 microns and observed a dose-dependent antitumor effect. No significant difference was observed, however, between 2 and 4 mg eq CDDP/kg dose levels (p > 0.05). From these results, we concluded that microsphere size and CDDP dose were strongly correlated with the augmentation of antitumor effect of chitin-containing CDDP albumin microspheres used in chemo-embolization therapy via the hepatic artery.
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Y
Y
Nishioka
S
S
Kyotani
M
M
Okamura
S
S
Ohnishi
Y
Y
Yamamoto
Y
Y
Kawashima
S
S
Tanada
T
T
Nakamura
D000418:Albumins; D000818:Animals; D016461:Chemoembolization, Therapeutic; D002686:Chitin; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010984:Platinum / Q000097:blood / Q000378:metabolism; D011817:Rabbits
D000418:Albumins; D004337:Drug Carriers; D002686:Chitin; D010984:Platinum; D002945:Cisplatin