Antineoplastic activity of sterically stabilized alkylphosphocholine liposomes in human breast carcinomas.
New sterically stabilized liposomes derived from the antitumor agent hexadecylphosphocholine with reduced uptake by the mononuclear phagocyte system and improved antitumor activities were developed and tested. The bilayer of such sterically stabilized liposomes consists of hexadecylphosphocholine, cholesterol and polyethylene glycol-linked phosphoethanolamine. The measurement of carbon clearance in mice shows that these stabilized liposomes, in contrast to conventional alkylphosphocholine liposomes, are not largely engulfed by the mononuclear phagocyte system. Their therapeutic activity on experimental human breast carcinomas MaTu. MT-1 and MT-3 was tested in nude mice. Especially in the MaTu models the sterically stabilized hexadecylphosphocholine liposomes resulted in significantly reduced tumor growth in comparison to conventional hexadecylphosphocholine liposomes or free hexadecylphosphocholine. The enhanced therapeutic efficacy of sterically stabilized hexadecylphosphocholine liposomes is probably related to the extended circulation time of the formulation and its accumulation in tumors.
Arndt
D
D
Max-Delbrück-Center of Molecular Medicine, Berlin-Buch, Germany.
Zeisig
R
R
Eue
I
I
Sternberg
B
B
Fichtner
I
I
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol; D004983:Ethanolamines; D006801:Humans; D008081:Liposomes; D008657:Metabolic Clearance Rate; D051379:Mice; D010713:Phosphatidylcholines; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D011092:Polyethylene Glycols; D011960:Receptors, Estrogen; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004983:Ethanolamines; D008081:Liposomes; D010713:Phosphatidylcholines; D011960:Receptors, Estrogen; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C039128:miltefosine; C005448:phosphorylethanolamine; D002784:Cholesterol