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

Abstract

The presence of particular surface carbohydrate modifications is shown to affect dramatically the stability and tissue specificity of unilamellar distearoyl phosphatidylcholine vesicles in mice. Use of the γ-ray probe (111)In(3+) permits analysis of tissue distributions by standard γ 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 intravenous injection followed by concentration of intact vesicles in the liver and spleen. Vesicles bearing 6-aminosugar residues are found to concentrate in the axillary space in aggregates of polymorphonuclear leukocytes when administered subcutaneously. The in vivo stability of 6-aminomannose-labeled vesicles is substantially greater after intravenous or subcutaneous 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.

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