UPTAKE OF LIPOSOMES AND LIPOSOME-ENCAPSULATED MURAMYL DIPEPTIDE BY HUMAN PERIPHERAL-BLOOD MONOCYTES

Abstract

The interaction of multilamellar liposomes with human peripheral blood monocytes, cultured in vitro, were examined. Phagocytic engulfment is the principal mechanism by which the liposomes are taken up by these cells. Studies with radiolabeled liposomes revealed that they are taken up by monocytes as intact structures. The uptake is temperature sensitive and is affected by inhibitors of glycolysis and of microfilament activity. Monocytes take up negatively charged vesicles more rapidly than positively charged (3-fold) vesicles or neutral vesicles (5-fold). Increase in negative charge of liposomes enhances their uptake by the cells, but increased saturation of the phospholipids results in decreased uptake. Liposomes provide an effective means of enhancing the uptake of MDP [muramyl-L-alanyl-D-isoglutamine] derivatives (3H-norMDP) by monocytes, with a 20-fold greater uptake of liposome encapsulated drug than of the free compound. Monocytes do not degrade the 3H-norMDP that they have internalized and radiolabel is only slowly released from the cells. These observations suggest a pharmacokinetic basis for the use of lipid vesicles as a system for the delivery of immunomodulating drugs to monocytes.