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.

Abstract:

: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.

journal_name

Int J Cancer

authors

Tokuda K,Natsugoe S,Shimada M,Kumanohoso T,Baba M,Takao S,Nakamura K,Yamada K,Yoshizawa H,Hatate Y,Aikou T

doi

10.1002/(sici)1097-0215(19980529)76:5<709::aid-ijc

subject

Has Abstract

pub_date

1998-05-29 00:00:00

pages

709-12

issue

5

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19980529)76:5<709::AID-IJC

journal_volume

76

pub_type

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