A dried preparation of liposomes containing muramyl tripeptide phosphatidylethanolamine as a potent activator of human blood monocytes to the antitumor state.
Studies were performed on the activation of human blood monocytes to the antitumor state by a dried preparation of multilamellar vesicle (MLV) liposomes in which synthetic muramyl tripeptide phosphatidylethanolamine (MTP-PE) was inserted directly into the liposome membrane. Dried liposomes composed of synthetic phospholipids [phosphatidylcholine (PC) and phosphatidylserine (PS) in a molar ratio of 7:3] were prepared by lyophilization. Dried liposome-MTP-PE was found to be superior in several ways to free desmethyl muramyl dipeptide (norMDP) or conventional liposome-MTP-PE, prepared immediately before use. First, dried liposome-MTP-PE was stable and strongly activated monocytes when stored for over 3 months in a freezer at -20 degrees C or even in suspension at 4 degrees C. Second, human monocytes in suspension, as well as in the adherent form, were activated to the tumoricidal state by interaction for at least 4 h with the dried preparation of liposome-MTP-PE. Third, monocytes activated with the dried liposome-MTP-PE or conventionally prepared liposome-MTP-PE maintained their tumoricidal activity for a longer period (4 days) than those activated with free norMDP. These results indicate that the dried preparation of liposome-MTP-PE can be stored for a long time, has a reproducible effect that can be standardized and should be valuable for in situ activation of human monocytes to the tumoricidal state, which is associated with eradication of cancer metastases.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004356:Drug Storage; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000494:pharmacology; D013535:Suspensions; D013997:Time Factors
D008081:Liposomes; D010714:Phosphatidylethanolamines; D013535:Suspensions; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine