Phagocytosis of carbohydrate-modified phospholipid vesicles by macrophage.

Wu, Po-Shun; Tin, George W.; Baldeschwieler, John D.

doi:10.1073/pnas.78.4.2033

Cited by 21 publications

(10 citation statements)

References 39 publications

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“…L-a-Distearoyl phosphatidylcholine (Ste2PtdCho) from Calbiochem and cholesterol (Chol) from Sigma were used without further purification. Mannosyl, aminomannosyl, and aminogalactosylderivatives ofChol [6-(5-cholesten-3/3-yloxy)hexyl 1-thio-a-D-mannopyranoside (ManChol), 6-(5-cholesten-316 yloxy)hexyl 6-amino-6-deoxy-1-thio-a-D-mannopyranoside (NH2ManChol), and 6-(5-cholesten-3f3-yloxy)hexyl 6-amino-6-deoxy-l-thio-,f-D-galactopyranoside (NH2GalChol), respec- (5)(6)(7)(8)(9). Briefly, a lipid mixture was prepared by mixing Ste2PtdCho, Chol, NH2ManChol (or NH2GalChol), and A23, 2:0.5:0.5:0.004 (mol/mol) or as otherwise specified.…”

Section: Methodsmentioning

confidence: 99%

“…Freshly prepared (or aged) liposomes were added to the Petri dish cultures to an activity of --15,000 cpm ("'30 ,g of P), and phagocytosis was measured as described (9). RESULTS Turbidity.…”

Section: Methodsmentioning

confidence: 99%

“…Cells from the peritoneal cavity of unstimulated male Swiss-Webster mice (25-30 g) were harvested as described (9).…”

Section: Methodsmentioning

confidence: 99%

“…We have recently found that modification of the surface of distearoyl phosphatidylcholine vesicles by specific synthetic glycolipid determinants can affect the rate of uptake of these vesicles by mouse peritoneal macrophage in vitro and the differential tissue distribution of these vesicles in vivo in mice (5)(6)(7)(8)(9). However, small sonicated vesicles are thermodynamically unstable, and the properties of these vesicles can change significantly in the temperature range at which phase transitions occur (10)(11)(12).…”

mentioning

confidence: 99%

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Effect of surface modification on aggregation of phospholipid vesicles.

Wu¹,

Tin²,

Baldeschwieler³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Phospholipid vesicles have been extensively investigated because of their usefulness as models for biological membranes and their potential application as carriers for drug delivery. However, preparations of small sonicated vesicles tend to aggregate and fuse (on storage at room temperature and at 4°C), resulting in significant changes in turbidity, rate of uptake by macrophage, and proton NMR linewidths. By modification of the surface of phospholipid vesicles with charged groups such as 11-aminogalactose that extend significantly from the vesicle surface, it is possible to obtain preparations that are stable for >7 days.Phospholipid vesicles have been extensively investigated because of their usefulness as models for biological membranes and their potential application as carriers for drug delivery (1-4). We have recently found that modification of the surface of distearoyl phosphatidylcholine vesicles by specific synthetic glycolipid determinants can affect the rate of uptake of these vesicles by mouse peritoneal macrophage in vitro and the differential tissue distribution of these vesicles in vivo in mice (5-9). However, small sonicated vesicles are thermodynamically unstable, and the properties of these vesicles can change significantly in the temperature range at which phase transitions occur (10-12). In particular, small sonicated vesicles tend to aggregate and fuse below the phase transition temperature, resulting in an increase in vesicle size as a function oftime (13-16). As these changes will ultimately affect the practical usefulness of phospholipid vesicles for drug delivery, we report in this paper studies of the effect of surface modification on the aggregation and fusion of phospholipid vesicles and on the rate of uptake of these vesicles by mouse peritoneal macrophage. MATERIALS AND METHODSMaterials. L-a-Distearoyl phosphatidylcholine (Ste2PtdCho) from Calbiochem and cholesterol (Chol) from Sigma were used without further purification. Mannosyl, aminomannosyl, and aminogalactosylderivatives ofChol [6-(5-cholesten-3/3-yloxy)hexyl 1-thio-a-D-mannopyranoside (ManChol), 6-(5-cholesten-316 yloxy)hexyl 6-amino-6-deoxy-1-thio-a-D-mannopyranoside (NH2ManChol), and 6-(5-cholesten-3f3-yloxy)hexyl 6-amino-6-deoxy-l-thio-,f-D-galactopyranoside (NH2GalChol), respectively] were synthesized at Merck. [oleate-1-'4C]Cholesteryl oleate (specific activity, 51 Ci/mol; 1 Ci = 3.7 x 10'°becque-rels) was purchased from New England Nuclear.Newborn calf serum, medium-199, and penicillin/streptomycin were purchased from Microbiological Associates (Los Angeles, CA) and plastic Petri dishes (35 x 10 mm) were obtained from Falcon. D20 (99.8% D) was purchased from Aldrich.Preparation of Liposomes. Small unilamellar vesicles were prepared according to the method ofMauk and colleagues (5-9). Briefly, a lipid mixture was prepared by mixing Ste2PtdCho, Chol, NH2ManChol (or NH2GalChol), and A23, 2:0.5:0.5:0.004 (mol/mol) or as otherwise specified. The mixture was dried in vacuum overnight and then probe sonicated in phosph...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Cells from the peritoneal cavity of unstimulated male Swiss-Webster mice (25-30 g) were harvested as described (9).…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Effect of surface modification on aggregation of phospholipid vesicles.

Wu¹,

Tin²,

Baldeschwieler³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C.. §1734 solely to indicate this fact. as described (14). Vesicle aggregation and fusion in buffered solution was monitored by light scattering (15).…”

mentioning

confidence: 99%

Stability of carbohydrate-modified vesicles in vivo: comparative effects of ceramide and cholesterol glycoconjugates.

Wu¹,

Wu²,

Tin³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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The stability and tissue distribution of lipid vesicles modified at the surface by the incorporation ofeither a galactosyl ceramide (GalCer)'or a galactosyl'cholesterol (GalChol) glycoconjugate have been studied in. mice by measuring the release of vesicle-entrapped "'1In. Although the tissue distributions of both vesicle types were similar, the GalCer-containing vesicles were markedly less stable than those. prepared with GalChol, whether administered orally or by intraperitoneal injection. Physical characterization of the vesicles in vitro suggests that the increased disruption rate for GalCer vesicles in vivo is related to. structural instabilities induced by the cerebroside, which can then result in either an increased rate of vesicle uptake by tissues or a greater susceptibility to lysis. These studies demonstrate the importance ofthe nonpolar anchoring groups in determining the fate of surface-modified vesicles in vivo.The targeting ofencapsulated agents, such as drugs or enzymes, to specific tissues is one of the goals in the development of liposomes as exogenous delivery systems. To achieve this result, a number of strategies have been attempted, including the addition ofcharged lipids to neutral vesicles (1), the covalent binding of antibodies to vesicle surfaces (2), and the use oflocalized hyperthermia to induce phase transitions in synthetic liposomes (3). The finding that mammalian hepatocyte surfaces contain a galactose-specific glycoprotein binding site (4) has led to studies on the usefulness ofcarbohydrate-modified vesicles in targeting encapsulated materials (5-7). Initial work has shown great promise (7), leading to further investigation ofvariables that can affect the system. Due to the amphiphilic nature of vesicle bilayers, it is convenient to incorporate polar carbohydrate molecules by attaching them to nonpolar lipid groups. In view' of the importance of lipid shape to vesicle structure (8), it is likely that the choice of lipid conjugate or anchoring group will, in addition to the type of carbohydrate used, affect the fate of modified vesicles in vivo. In the present communication; we report studies of carbohydrate-modified vesicles containing glycolipids differing in the structure oftheir nonpolar group. The results, comparing the effects of N-stearoyl-DL-dihydrogalactocerebroside (galactosyl ceramide, GalCer, II) with those of 6-(5-cholesten-3f-yloxy)hexyl-l-thio-(3-D-galactopyranoside (galactosyl cholesterol, GalChol, I) demonstrate the importance of the carbohydrate anchoring group in maintaining stable vesicles in vivo.

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