Targeting of lipid vesicles: specificity of carbohydrate receptor analogues for leukocytes in mice.

Abstract

The presence of particular surface carbohydrate modifications dramatically affects the stability and tissue specificity of unilamellar distearoyl phosphatidylcholine vesicles in mice. Use of the .gamma.-ray probe 111In3+ permits analysis of tissue distributions by standard .gamma.-counting techniques and determination of the structural integrity of the vesicles by perturbed angular correlation spectroscopy. Addition of a 6-aminomannose derivative of cholesterol to the lipid bilayer produces initial retention of high levels of intact vesicles in the lung after i.v. injection followed by concentration of intact vesicles in the liver and spleen. Vesicles bearing 6-amino sugar residues concentrate in the axillary space in aggregates of polymorphonuclear leukocytes when administered s.c. The in vivo stability of 6-aminomannose-labeled vesicles is substantially greater after i.v. or s.c. administration than that observed for any other system examined. The dose-response effects observed with surface modifications indicate that a particular receptor topography is important in the mechanism leading to transport and destruction of these vesicles. [Liposomes are being investigated as possible carriers for therapeutic and diagnostic agents.].