[The development of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma].
We developed chitin-containing cisplatin (CDDP) albumin microspheres (MS). We also investigated physical properties of MS in vitro, anti-tumor effect of MS in VX2 tumor model rabbits in vivo and clinical evaluation of MS. The CDDP contents, specific surface areas and yield of MS increased with an increase in the concentration of chitin. These findings suggest that accumulation of chitin on the surface of microsphere was the cause of expansion of the coated area as the concentration of chitin increased. In vitro CDDP releases decreased as the concentration of chitin increased. The initial burst effect of the drug was to be controlled by the increase of concentration of chitin. The chitin-containing CDDP microspheres showed similar CDDP release patterns irrespective of the concentration of chitin between 1 and 6 h after the administration of CDDP microspheres. After 6 h, the blood Pt levels increased with an increase in the concentration of CDDP microspheres suggesting a significant effect of the concentration of chitin on microsphere decomposability in vivo. Tumor growth rate was increasingly suppressed as the concentration of chitin increased. Clinical findings indicated that antitumor activity of chitin-containing CDDP albumin microspheres would have a chemoembolic effect by embolizing the hepatic artery. In the tumor and necrosis portions phagocytosis of microspheres by macrophage-like giant cell was shown. Consequently, the biocompatibility and decomposable properties of chitin-containing CDDP albumin microspheres were demonstrated.
Kyotani
S
S
Department of Pharmacy, Kochi Medical School Hospital, Okoho-cho, Nankoku, Kochi 783-8505, Japan.
Nishioka
Y
Y
D000418:Albumins; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D002686:Chitin; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D008863:Microspheres; D010316:Particle Size; D011817:Rabbits; D014018:Tissue Distribution
D000418:Albumins; D000970:Antineoplastic Agents; D002686:Chitin; D002945:Cisplatin