The influence of size and composition on the cholesterol mobilizing properties of liposomes in vivo.
As part of a study into the antiatherogenic properties of phospholipid liposomes we have investigated the capacity of a variety of preparations to increase plasma cholesterol concentrations in mice. Large unilamellar vesicles, composed of egg phosphatidylcholine, were found to be approximately twice as effective at mobilizing cholesterol than sonicated vesicles of the same composition. For egg phosphatidylcholine liposomes the change in plasma cholesterol profile is proportional to the residence time of vesicles in the circulation. Large unilamellar vesicles with a diameter of approx. 100 nm accumulate the most sterol in the animal model tested here, reaching equimolar concentrations with phospholipid after 24 h. Gel-state vesicles gave rise to a smaller increase in plasma cholesterol compared to liquid-crystalline vesicles. Our data indicate that, in vivo, net transfer of cholesterol into liposomes occurs more extensively from the lipoprotein cholesterol pool than from the erythrocyte cell membrane pool. This is consistent with the hypothesis (Williams, K.J., Werth, V.P. and Wolff, J.A. (1984) Perspect. Biol. Med. 27, 417-431) that liposomes enhance reverse cholesterol transport by generating cholesterol-poor HDL particles that can extravasate and promote more sterol efflux from peripheral tissues.
Rodrigueza
W V
WV
Liposome Research Unit, Vancouver, British Columbia, Canada.
Pritchard
P H
PH
Hope
M J
MJ
D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000737:chemistry* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol