Potential value of cetylmannoside-modified liposomes as carriers of macrophage activators to human blood monocytes.
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 endotoxin-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 U/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.
Yamashita
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Department of Pharmacodynamics and Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Tokushima.
Sone
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Ogura
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Kiwada
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D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D016215:Macrophage-Activating Factors / Q000008:administration & dosage*; D008358:Mannose / Q000494:pharmacology; D008362:Mannosides / Q000494:pharmacology*; D008545:Melanoma; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D014407:Tumor Cells, Cultured
D008081:Liposomes; D016215:Macrophage-Activating Factors; D008362:Mannosides; C069589:cetylmannoside; D008358:Mannose