Potential Value of Cetylmannoside-modified Liposomes as Carriers of Macrophage Activators to Human Blood Monocytes

Abstract

The present study was undertaken to examine the potential value of cetylmannoside‐modified multilamellar liposomes (Man‐MLV) as carriers for transfer of macrophage activators to blood monocytes. Highly purified blood monocytes were isolated by centrifugal elutriation from healthy donors under cndotox in‐free conditions. Freshly prepared monocytes phagocytosed Man‐MLV to a lesser extent than monocyte‐derived macrophages, but they took up Man‐MLV much more effectively than control liposomes without cetylmannoside (control MLV). Phagocytosis of Man‐MLV, but not control MLV by monocytes was inhibited by addition of D‐mannose, but not of D‐galactose. Desmethyl‐muramyl dipeptide (norMDP) entrapped in Man‐MLV was far more effective than norMDP entrapped in MLV in activating monocytes to the tumoricidal state. The effect of encapsulation of recombinant human macrophage colony‐stimulating factor (M‐CSF) in Man‐MLV on prolongation of survival of monocytes was examined. Blood monocytes that had been incubated for up to 21 days with Man‐MLV containing 5–20 U of M‐CSF per ml were effective in prolonging monocyte survival, but monocytes that had been incubated in medium with less than 50 If/ml of M‐CSF or with control MLV containing 5–10 U of M‐CSF showed no increase of monocyte survival over that in medium alone. Addition of rabbit anti‐M‐CSF antiserum did not affect survival prolongation of monocytes by M‐CSF encapsulated in Man‐MLV. We conclude that liposomes modified with cetylmannoside are far more effective than unmodified liposomes as a carrier to deliver biological response modifiers to human blood monocytes.