Abstract
The present study evaluated the in vivo biological activity of synthetic muramyl tripeptide, CGP 19835A, when encapsulated into phosphatidylcholine liposomes (POPC-19835A) and administered as an p.o. immunomodulator to BALB/c mice. Liposomes were rapidly absorbed in the intestine and reached the systemic circulation within 4 h. Alveolar macrophages harvested from the lungs of mice 24 h after a single p.o. feeding of POPC-19835A were tumoricidal toward syngeneic murine renal cell carcinoma target cells. Repeated daily feedings with POPC-19835A generated sustained activation of the alveolar macrophages. Activation of peritoneal macrophages to the tumoricidal state required at least three daily feedings of POPC-19835A. In vitro studies demonstrated the release of tumor necrosis factor alpha and interleukin 6 by macrophages activated by POPC-19835A in the presence of gamma-interferon. Interleukin 1 and nitric oxide were not induced in macrophages by this liposomal preparation. Daily administration of POPC-19835A after i.v. injection of renal cell carcinoma tumor in BALB/c mice inhibited the development of experimental lung metastasis and confirmed the potential role of long-term therapy with this new p.o. immunomodulator.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
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Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacokinetics
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
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Adenocarcinoma / therapy*
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Adjuvants, Immunologic / administration & dosage
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Adjuvants, Immunologic / pharmacokinetics
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Adjuvants, Immunologic / pharmacology*
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Administration, Oral
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Animals
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Drug Carriers
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Female
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Immunotherapy
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Interleukin-1 / metabolism
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Interleukin-6 / metabolism
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Kidney Neoplasms / therapy*
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Liposomes / administration & dosage
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Liposomes / pharmacokinetics
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Macrophage Activation*
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Macrophages, Alveolar / drug effects
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Macrophages, Alveolar / metabolism
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Macrophages, Alveolar / physiology*
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Macrophages, Peritoneal / drug effects
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Macrophages, Peritoneal / metabolism
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Macrophages, Peritoneal / physiology*
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Male
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Mice
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Mice, Inbred BALB C
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Phosphatidylethanolamines / administration & dosage
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Phosphatidylethanolamines / pharmacokinetics
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Phosphatidylethanolamines / pharmacology*
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Specific Pathogen-Free Organisms
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Tissue Distribution
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Adjuvants, Immunologic
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Drug Carriers
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Interleukin-1
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Interleukin-6
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Liposomes
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Phosphatidylethanolamines
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Tumor Necrosis Factor-alpha
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mifamurtide
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Acetylmuramyl-Alanyl-Isoglutamine