Design and testing of a new cisplatin form using a base material by combining poly-D,L-lactic acid and polyethylene glycol acid against peritoneal metastasis.
Microspheres containing cisplatin (CDDP) embedded in poly-d,l-lactic acid (PLA) and polyethylene glycol acid (CDDP-PPMS) were developed to improve treatment of malignant effusions. In vitro studies demonstrated that CDDP was released continuously for more than 4 weeks from CDDP-PPMS without initial burst. CDDP-PPMS was compared with CDDP aqueous solution (CDDP-SOL) by i.p. administration in rats for 1) tissue distribution, 2) toxicity and 3) therapeutic effects against Yoshida sarcoma. We found that the CDDP concentration in the omentum was maintained at a higher level than in the CDDP-SOL group, while the particles of CDDP-PPMS were observed in the stomata of the omentum by electron microscopy. Concentrations of CDDP in the lung, liver, kidney and blood were lower in the CDDP-PPMS group than in the CDDP-SOL group. All rats given CDDP-PPMS containing < or = 28 mg/kg were alive, whereas in the CDDP-SOL group, all rats given > or = 16 mg/kg died from side effects. The LD50 of CDDP-PPMS and CDDP-SOL were 32.8 and 14.8 mg/kg, respectively. The survival of rats with peritoneal metastasis was better in the CDDP-PPMS group than in the CDDP-SOL group.
Tokuda
K
K
First Department of Surgery, Kagoshima University School of Medicine, Japan.
Natsugoe
S
S
Shimada
M
M
Kumanohoso
T
T
Baba
M
M
Takao
S
S
Nakamura
K
K
Yamada
K
K
Yoshizawa
H
H
Hatate
Y
Y
Aikou
T
T
D000818:Animals; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D007274:Injections, Intraperitoneal; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D009368:Neoplasm Transplantation; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D014018:Tissue Distribution
D014677:Pharmaceutical Vehicles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D002945:Cisplatin