Blood lipid bilayers

The half-life of liposomes administered in the blood stream is affected by the composition, size, charge, and fluidity. Liposomes with a small size or with a rigid lipid bilayer have a longer half-life (38 9). Large liposomes administered iv tend to accumulate at a lymph node near the injected site. This tendency can be useful for preventing metastases. Liposomes which pass through the lymph node have a tendency to accumulate in the RES, such as the liver and spleen (40,41). The disposition of liposomes is altered by the dose of liposomes as well as size or lipid composition of liposomes. Cholesterol rich liposomes are cleared slower due to... 

Carotenoids are also present in animals, including humans, where they are selectively absorbed from diet (Furr and Clark 1997). Because of their hydrophobic nature, carotenoids are located either in the lipid bilayer portion of membranes or form complexes with specific proteins, usually associated with membranes. In animals and humans, dietary carotenoids are transported in blood plasma as complexes with lipoproteins (Krinsky et al. 1958, Tso 1981) and accumulate in various organs and tissues (Parker 1989, Kaplan et al. 1990, Tanumihardjo et al. 1990, Schmitz et al. 1991, Khachik et al. 1998, Hata et al. 2000). The highest concentration of carotenoids can be found in the eye retina of primates. In the retina of the human eye, where two dipolar carotenoids, lutein and zeaxan-thin, selectively accumulate from blood plasma, this concentration can reach as high as 0.1-1.0mM (Snodderly et al. 1984, Landrum et al. 1999). It has been shown that in the retina, carotenoids are associated with lipid bilayer membranes (Sommerburg et al. 1999, Rapp et al. 2000) although, some macular carotenoids may be connected to specific membrane-bound proteins (Bernstein et al. 1997, Bhosale et al. 2004). 

Several glycoproteins, which are present in the lipid bilayer of the virus, are necessary for infection. One is known as GP120. It binds to the CD4 protein on the surface of the Th lymphocyte (i.e. the CD4-I- ceU). This initiates fusion with the plasma membrane of the CD4-I- cell so that the viral RNA and its proteins enter the cell (i.e. it infects the CD4-t cell). The original infection probably occurs in the peripheral circulation but the lymphocytes will be transported by the blood to the spleen, other lymph nodes and the brain, where the microglia become infected (Figure 17.46). 

An ability to penetrate lipid bilayers is a prerequisite for the absorption of drugs, their entry into cells or cellular organelles, and passage across the blood-brain barrier. Due to their amphiphilic nature, phospholipids form bilayers possessing a hydrophilic surface and a hydrophobic interior (p. 20). Substances may traverse this membrane in three different ways. 

Orally administered drugs partition into the lipid bilayer in the process of diffusing across the apical and basolateral membranes of the intestinal brush border cells into the blood, as illustrated in Figure 2. About 1800 such drugs are commercially available. A small surface area of the polar parts of the drug molecule generally favors entry into the hydrophobic interior of... 

Deuterium (2H). The natural abundance is very low so that use of 2H-labeled compounds is practical for study of metabolism, e.g., for following an 2H label in glucose into products of fermentation455 or in mammalian blood flow 456 Deuterium NMR has been used extensively to study lipid bilayers (Chapter 8). 

It was found that unloaded PEBPBLA micelles cause no hemolysis, even at a level of 0.70 mg/mL. PECb-PBLA has an extremely low critical micelle concentration (Kwon et al., 1993), and thus, there is little monomeric PBEPBLA for the lysis of lipid bilayer membranes. In addition, PEO-bPBLA micelles may break apart slowly to monomers. The lack of hemolytic activity of PEO-bPBLA contrasts strongly with other amphiphiles used for drug solubilization and intravenous drug administration. Sodium deoxycholate causes 100% hemolysis at a level of 0.32 mg/mL. This is due to disruption of lipid bilayer membranes of red blood cells. 

The reported effects of surfactants on membrane permeability have been observed by other authors using a different approach. Rege et al. [32] studied the inhibition activity of non-ionic surfactants on P-glycoprotein (P-gp) efflux and the relationship between inhibition and membrane fluidity. Tween 80 and Cremophor inhibited P-gp. These inhibition effects could be related to their effects on membrane fluidity, as these surfactants fluidized cell lipid bilayers. This fluidification mechanism could be related to the increase in membrane polarity that we observed with synthetic surfactants in our experiments and it has been reported by other authors as a possible explanation for the inhibition effects of surfactants on P-gp efflux in the blood-brain barrier [33]. 

On the other hand, PAMPA is a purely artificial method and PAMPA membranes do not reassemble real lipid bilayer structures as barriers for permeation but much thicker barriers. The thickness and material of the supporting PVDF filters also influences artificially the permeation of compounds depending on the lipophilicity of the compounds more than the thin polycarbonate filter does in CACo2 experiments. Also the best choice of membrane constituents for PAMPA experiments is still under investigation and it seems that it will depend a lot on the goal of the PAMPA experiment which membrane is used (e.g. blood brain barrier permeation or intestinal absorption). One has to take into account that PAMPA today is a summary term on a lot of different methods applied in different laboratories using different membrane constituents, sink conditions, permeation times etc., which makes inter laboratory comparison difficult. 

In 1925 Evert Gorter and F. Grendel estimated that the lipids from erythrocytes (red blood cells), when spread as a monomolecular layer, cover an area nearly twice the surface area of the cells. The amount of lipid present is apparently sufficient to form a double layer in the membrane. Moreover, the penetration of a series of substances across membranes often depends on the relative lipid solubility of the molecules. This circumstantial evidence led to the concept of a biological membrane composed primarily of a lipid bilayer. 

Brain vascular endothelial cells are linked by tight junction proteins creating high-resistance junctions between cells that effectively prevent the movement of hydrophilic substances, including electrolytes, such as Na and K+. Water moves across the lipid bilayer of endothelial cells through simple diffusion and vesicular transport (Tait et al., 2008). However, specialized water channels are formed by molecules called aquaporins (AQPs), which are highly expressed in blood-brain interfaces to facilitate the transport of water across cell membranes. 

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