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

Roman Perez-Soler, A. R. Khokhar, P. Claringbold, L. P. Kasi, G. Lopez-Berestein

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Abstract

Multilammer 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- platinum (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 μg CDDP and L-CPDP/ml but not at concentrations of 1 and 5 μg/ml. The differences in plasma clearance of (99m)Tc-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>.05; liver uptake % of control: 87, 96, and 104, respectively: P>.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.

Original languageEnglish (US)
Pages (from-to)1137-1143
Number of pages7
JournalJournal of the National Cancer Institute
Volume77
Issue number5
StatePublished - 1986
Externally publishedYes

Fingerprint

Leukemia L1210
Monocytes
Macrophages
Maximum Tolerated Dose
Peritoneal Macrophages
Poisons
Liver
bis(cyclopentenecarboxylato)-1,2-diaminocyclohexane-platinum(II)
((1R,2R)-1,2-diaminocyclohexane)platinum(II)
Phosphatidylcholines
Liposomes
Superoxides
Cisplatin
Appointments and Schedules
RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{a39bedbfdc9f4f9b83effa16eacaef99,
title = "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",
abstract = "Multilammer 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- platinum (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 μg CDDP and L-CPDP/ml but not at concentrations of 1 and 5 μg/ml. The differences in plasma clearance of (99m)Tc-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>.05; liver uptake {\%} of control: 87, 96, and 104, respectively: P>.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.",
author = "Roman Perez-Soler and Khokhar, {A. R.} and P. Claringbold and Kasi, {L. P.} and G. Lopez-Berestein",
year = "1986",
language = "English (US)",
volume = "77",
pages = "1137--1143",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - 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

AU - Perez-Soler, Roman

AU - Khokhar, A. R.

AU - Claringbold, P.

AU - Kasi, L. P.

AU - Lopez-Berestein, G.

PY - 1986

Y1 - 1986

N2 - Multilammer 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- platinum (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 μg CDDP and L-CPDP/ml but not at concentrations of 1 and 5 μg/ml. The differences in plasma clearance of (99m)Tc-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>.05; liver uptake % of control: 87, 96, and 104, respectively: P>.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.

AB - Multilammer 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- platinum (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 μg CDDP and L-CPDP/ml but not at concentrations of 1 and 5 μg/ml. The differences in plasma clearance of (99m)Tc-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>.05; liver uptake % of control: 87, 96, and 104, respectively: P>.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.

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VL - 77

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EP - 1143

JO - Journal of the National Cancer Institute

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