US EPA

8714876 

Journal Article 

In vitro antitumor activity, intracellular accumulation, and DNA adduct formation of cis [((1 R, 2 R)-1, 2-cyclohexanediamine-N, N′ bis (myristato)] platinum (II) suspended in Lipiodol 

Miyazawa, K; Kishimoto, S; Fukushima, S; Takeuchi, Y 

1999 

14 

5 

401-405 

English 

10.2745/dds.14.401 

Cis [((1 R, 2 R) -1, 2-cyclohexanediamine-N, N') bis(myristato)] platinum (II) (SM-11355) is a plati num complex under development that targets pri mary hepatocellular carcinoma using Lipiodol as a carrier. The present study attempted to clarify the relationship between the sustained release of SM- 11355 suspended in Lipiodol (SM-11355/Lipiodol) and the adduct formation of the released compound to nuclear DNA as a target, using an assay system capable of coexisting with the drugs contained in Lipiodol and tumor cells. SM-11355/Lipiodol and CDDP suspended in Lipiodol (CDDP/Lipiodol) showed cytotoxic activity against rat ascite he patoma AH-109 A cells in a dose-dependent man ner. SM-11355/Lipiodol showed a sustained release into the culture medium over the course of a 7-day drug exposure. Following the exposure of CDDP/Lipiodol, the platinum concentration in the culture medium was at its maximum on the first day and remained constant thereafter. Intracellular plati num uptake and adduct formation to nuclear DNA were dependent on the release characteristic of each drug suspension. Although cyclohexane-1, 2-diamineplatinum (II) diiodide (DPI) and cyclohex ane-1, 2-diamineplatinum (II) dichloride (DPC), which are hypothesized as the release compound from SM-11355/Lipiodol, were taken up by cells, only DPC detected DNA adduct formation. Thus, this study observed that SM-11355/Lipiodol shows a sustained release of cytotoxic compounds, like DPC that bind to DNA and subsequently show the cytotoxic activity as SM-11355/Lipiodol. 1999, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved. 

cisplatin; cytotoxicity; DNA adduct; Lipiodol; SM-11355