Antitumor activity of a new series of platinum complexes: trans(+/-)-1,2-cyclohexanediammineplatinum(II) conjugated to acid polysaccharides.
Complexes with trans(+/-)-1,2-cyclohexanediammineplatinum(II) conjugated to acid polysaccharides were synthesized and their antitumor activities were tested in female CDF1 mice with intraperitoneal leukemia L1210 cells. Platinum was released from the polymers under physiological conditions, with half-lives from 3.3 to 19.3 h. A hyaluronic acid-supported complex was the most effective against the tumors (all six mice survived for 60 days). The group given a chondroitin polysulfate-supported complex had five survivors, the chondroitin sulfate A group also had five, the chondroitin sulfate C group had three and the heparan sulfate group had two. Part of the antitumor activity was due to increased efficacy of the polymers. The bioavailability of these complexes is high. Therefore, acid polysaccharides should be a good system for delivering antitumor platinum complexes.
Maeda
M
M
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Takasuka
N
N
Suga
T
T
Uehara
N
N
Hoshi
A
A
D000818:Animals; D002809:Chondroitin Sulfates / Q000138:chemical synthesis / Q000494:pharmacology; D002945:Cisplatin / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006207:Half-Life; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D010984:Platinum / Q000097:blood; D011134:Polysaccharides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*
D011134:Polysaccharides; D010984:Platinum; D002809:Chondroitin Sulfates; D002945:Cisplatin