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

Abstract

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.

Self-Assembly of Janus Oligomers into Onion-like Vesicles with Layer-by-Layer Water Discharging Capability: A Minimalist Model

“…Indeed, synthetic vesicles with tailored structures and specific functionalities have attracted considerable attention owing to their high potential in biological and nanomedical applications. However, vesicles are usually unstable because of the delicate balance required among the surface curvature energy, hydrophobic interactions between amphiphilic molecules, and the solvent effect. , In vivo , especially, vesicles cannot maintain their shape for long periods of time due to their interactions with surrounding proteins and blood constituents . Over the past two decades, the issue of stabilization of vesicles has been actively studied. − …”

“…10,11 In vivo, especially, vesicles cannot maintain their shape for long periods of time due to their interactions with surrounding proteins and blood constituents. 12 Over the past two decades, the issue of stabilization of vesicles has been actively studied. 13−15 Multilamellar vesicles 16−21 have been observed in polymeric and polymer−nanoparticle systems.…”

Polymerization-Induced Self-Assembly of Comb-like Amphiphilic Copolymers into Onion-like Vesicles

“…Fan et al studied interactions between liposomes and hydrophobic nanosheets to help future nanotoxicology studies of 2D nanomaterials . Synthetic vesicles are often used for drug and gene carriers due to their cavity structure, low toxicity, and functionality. − Compared with the small molecules, the polymers provide greater mechanical strength and more functions with different chemical modifications. , Even though the polymeric vesicles have good potential for practical applications, because of blood and protein, in vivo, it is also hard to maintain a stable vesicle structure . On the other hand, the poor preparation efficiency (solid content lower than 0.1%w/w) significantly blocks its commercial application to the traditional polymer self-assembly strategy .…”

“…12,13 Even though the polymeric vesicles have good potential for practical applications, because of blood and protein, in vivo, it is also hard to maintain a stable vesicle structure. 14 On the other hand, the poor preparation efficiency (solid content lower than 0.1%w/w) significantly blocks its commercial application to the traditional polymer self-assembly strategy. 15 How to improve the preparation efficiency and the stability of vesicles has always been an important research issue.…”

Functional cholesteryl binding agents: synthesis, characterization, and evaluation of antibody binding to modified phospholipid vesicles

“…The solvent was removed to leave a white solid. Chromatography on silica gel 60H (eluant 1% MeOH in CH2C12) yielded a pure product (0.80 g, 40%): mp 90-91 °C; XH NMR (CDClg) 3.4 (t, 2 H, HI of hexyl chain), 5.3 (m, 1 , H6), 9.7 (br, 1 H, acid proton); [a]25D -28.2 ± 0.2°(c 1.00, CHClg). Anal.…”