Effects on the monocyte-macrophage system and antitumor activity against L1210 leukemia of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane -platinum (II) encapsulated in multilamellar vesicles

• Published in: JNCI : Journal of the National Cancer Institute Vol. 77; no. 5; p. 1137
• Main Authors: Perez-Soler, R, Khokhar, A R, Claringbold, P, Kasi, L P, Lopez-Berestein, G
• Format: Journal Article
• Language: English
• Published: United States 01.11.1986
• Subjects: Animals; Cell Survival - drug effects; Cells, Cultured; Leukemia L1210 - drug therapy; Liposomes - administration & dosage; Liver - metabolism; Macrophages - drug effects; Metabolic Clearance Rate; Mice; Monocytes - drug effects; Organoplatinum Compounds - administration & dosage; Phagocytosis; Protein Biosynthesis; RNA - biosynthesis; Spleen - metabolism; Superoxides - metabolism
• ISSN: 0027-8874
• DOI: 10.1093/jnci/77.5.1137

Multilamellar vesicles (MLVs) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a molar ratio of 7:3 were used as carriers of cis-bis-cyclopentenecarboxylato-trans-R,R-1,2-diaminocyclohexane-p latinum (II) (CPDP). The encapsulation efficiency of liposomal CPDP (L-CPDP) was 87.6%, and its stability in normal saline at 14 days was 94.4%. The in vitro and in vivo effects on the function of the monocyte-macrophage system and the antitumor activity against L1210 leukemia were investigated in CD-1 and (C57BL/6J X DBA/2J)F1 mice. L-CPDP and cisplatin (CDDP) caused a comparable inhibition of murine-resident peritoneal macrophage (PM) protein and RNA synthesis and superoxide anion release. PM-mediated tumor cell cytotoxicity was completely inhibited at a concentration of 10 micrograms CDDP and L-CPDP/ml but not at concentrations of 1 and 5 micrograms/ml. The differences in plasma clearance of 99mTc-labeled MLV and phagocytic capacity of the liver among animals pretreated with the maximum tolerated doses of L-CPDP (25 mg/kg), empty liposomes, or CDDP (10 mg/kg) were not statistically significant (plasma clearance % of control: 105, 110, and 100, respectively: P greater than .05; liver uptake % of control: 87, 96, and 104, respectively: P greater than .05). At the maximum tolerated doses, the antitumor activity of L-CPDP against L1210 leukemia was similar to that of CDDP when a single dose was administered [median survival of treated mice/median survival of control mice X 100 (%T/C): 181 vs. 175] and slightly higher with the use of a triple-dose schedule (%T/C: 275 vs. 225). L-CPDP is easy to prepare, has a high-encapsulation efficiency and stability, is not more toxic than CDDP to the monocyte-macrophage system, and is at least as effective as CDDP against L1210 leukemia.