A dried preparation of liposomes containing muramyl tripeptide phosphatidylethanolamine as a potent activator of human blood monocytes to the antitumor state

Abstract

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.

Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid)

“…Freeze-dried liposomes containing MTP-PE were produced at Ciba-Geigy Ltd, (Basel, Switzerland) by mixing MTP-PE with synthetic phospholipids (phosphatidylcholine and phosphatidylserine at a 7 : 3 molar ratio) followed by lyophilization [27,30]. Before administration, 2.5 ml Ca 2+-and Mg2+-free phosphate-buffered saline (PBS) was added to vials containing lyophilized lipids and 1 mg MTP-PE.…”

Therapy of human ovarian cancer xenografts with intraperitoneal liposome encapsulated muramyl-tripeptide phosphoethanolamine (MTP-PE) and recombinant GM-CSF

“…As intraperitoneal or systemic administration of muramyl dipeptide or its analogues do not increase NK cell activity in the peritoneal cell population in mice (Talmadge 1985), we have assumed that the therapeutic effects described here are a consequence of the well documented effects of MTP-PE on macrophage function (Sone et al, 1980(Sone et al, , 1986b. This is also suggested by the clustering of peritoneal macrophages around tumour cells seen after injection of liposome encapsulated MTP-PE in to mice bearing the OS tumour.…”

Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages

“…Each value is the mean ± SD of triplicate samples firm these findings. Both liposome preparations were taken up by macrophages, and the presence of rlFN 7 increased this interaction [57,58]. CGP 31362 has a ner negative charge, which may explain why MLV containing this lipopeptide bound to macrophages to a higher extent than did MLV with CGP 19835 (Fig.…”