Intraperitoneal administration of hydroxyapatite particles as a drug carrier in rats bearing carcinomatous peritonitis

Carcinomatous peritonitis with resultant ascites can be the result of progression of gastrointestinal malignancies, especially of gastric origin. Various methods, including intraperitoneal and intravenous routs, have been tried to improve the efficacy of chemotherapeutic agents or biological response modifiers. Nevertheless, prognosis of such patients remains grim. Hydroxyapatite (HAp) has excellent compability with human tissues and has been used in orthopedic and dental procedures, and percutaneous devices for hyperalimentation. The drug carrier HAp particle has pores 23∼59 μm in diameter with a surface area of 25 m2/g. The efficacy of intraperitoneal administration of lentinan-loaded hydroxyapatite particles(HAp-LNTN) was explored using a Donryu rat model of tumor cell AH-130 carcinomatous peritonitis. The drug delivery system HAp-LNTN contained 200 mg HAp and 0.5 mg LNTN. The pharmacokinetics of LNTN following intraperitoneal administration of HAp-LNTN was studied. Serum levels of HAp-LNTN were elevated for 24hours compared with free-LNTN. Intraperitoneal administration of HAp-LNTN was effective in prolongation of survival of rats bearing AH-130 in the peritoneal cavity, day 35 to 55. Furthermore, the pharmocokinetics of carboplatin (CBDCA) following intraperitoneal administration of HAp-CBDCA was studied. Serum levels of CBDCA were higher in the HAp-CBDCA group compared to the free-CBDCA group from postdrug administration hour 6 until day 3. These results suggest that the efficacy of anticancer drugs is enhanced by utilizing HAp as a drug delivery system.