A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of chitin concentration on cis-diamminedichloroplatinum(II) albumin microsphere properties and antitumor effect in VX2 hepatocellular carcinoma model rabbits.
cis-Diamminedichloroplatinum(II) (CDDP) albumin microspheres were prepared with various chitin concentrations and microsphere CDDP contents, specific surface area, surface structure and other microsphere properties. CDDP release in vitro and the antitumor effect in VX2 tumor model rabbits were investigated. CDDP content was increased as the concentration of chitin increased; at a chitin concentration of 6.0% it was about 2 times that without chitin. Specific surface area also increased with chitin concentration. CDDP release rate from various microspheres in vitro was suppressed as chitin concentration increased. Thus, microsphere properties, especially surface structure, are affected by an increase in chitin concentration. In experiments in vivo, various microspheres were injected into the hepatic artery of VX2 hepatocellular carcinoma model rabbits, and the effects of the chitin concentration on the time course of blood platinum (Pt) level and the antitumor effect were assessed. The blood Pt concentration increased with increase in chitin concentration, with a maximum of 0.45 microgram/ml at a concentration of 6.0%, even 7 d following microsphere administration. Tumor growth was suppressed when the chitin concentration was increased. Tissue Pt concentrations also increased in the presence of chitin. These findings suggest that increasing the chitin concentration might promote microsphere decomposition and hence CDDP release in vivo, thus improving immunopotentiating activity and resulting in enhanced CDDP antitumor effect. The detailed mechanisms of the action, however remains to be studied.
Nishioka
Y
Y
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Kyotani
S
S
Okamura
M
M
Ohnishi
S
S
Yamamoto
Y
Y
Tanada
S
S
Nakamura
T
T
D000418:Albumins; D000818:Animals; D016461:Chemoembolization, Therapeutic; D002686:Chitin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D008863:Microspheres; D010984:Platinum / Q000032:analysis / Q000097:blood; D011817:Rabbits
D000418:Albumins; D002686:Chitin; D010984:Platinum; D002945:Cisplatin