Comparative interaction of free and liposome-encapsulated nor-muramyl dipeptide or muramyl tripeptide phosphatidylethanolamine (³H-labelled) with human blood monocytes

The purpose of this study was to analyse on biochemical and functional levels the interaction of free and liposome-encapsulated nor-muramyl dipeptide (nor-MDP) or muramyl tripeptide phosphatidylethanolamine (MTP-PE) with human peripheral blood monocytes. The activation of tumoricidal properties in monocytes by free MTP-PE required approximately 40-fold less material than free nor-MDP. Encapsulation of either MTP-PE or nor-MDP within multilamellar liposomes (MLV) increased the efficiency of the immunomodulators for activation of monocytes. The initial interaction of free ³H-nor-MDP or ³H-MTP-PE with monocytes was influenced by lipophilic derivatization, but neither derivatives exhibited characteristics of specific binding to the monocyte surface. The encapsulation of ³H-nor-MDP or ³H-MTP-PE within MLV increased uptake of both compounds by monocytes. The metabolic fate of MLV-entrapped ³H-nor-MDP was unaltered, but liposome encapsulation retarded the metabolism of ³H-MTP-PE. Collectively, the data suggest that the activation of monocytes by muramyl peptides results from an intracellular interaction which can be modulated by both lipophilic derivatization and/or liposome-encapsulation of this immunomodulator.