Abstract
Hydroxyapatite(HAp) particles has excellent compatibility with human tissue and can be safely administered into the peritoneal cavity of rats with no significant complications (Artif. Organs Today 3 : 185-192, 1994). We explored the possibility of HAp as a drug carrier for carboplatin using AH130 abdominal carcinomatosis. HAp particles are biodegradable following intraperitoneal administration(i. p.) and were taken up especially in greater omentum. The pharmacokinetics of HAp-CBDCA were examined using Donryu rat models with AH130 abdominal carcinomatosis. The platinum(Pt) levels in serum and ascites were higher in HAp-CBDCA i. p. than free-CBDCA i. v. groups. HAp-CBDCA i. p. were effective in prolonging the survival of rats model with AH130 abdominal carcinomatosis. HAp-CBDCA administration was experimentally confirmed to be safe. For the clinical application, HAp-CBDCA (HAp-particles : 5 g, CBDCA : 150 mg) was administered into the pleural cavity(i. pc.) at operation on the two advanced esophageal cancer and the pharmacokinetics of CBDCA were also examined. The serum levels of Pt were higher in the HAp-CBDCA(i. pc.) from 5 minute to 30 minute than those in the free-CBDCA(i. pc.). These results demonstrated the efficacy of HAp particles as a drug carrier for anticancer drugs, with ultimate improvement in overall survival.
