Blood, lipid complexes

Conventional liposomes and lipid complexes. Liposomes were used initially as a model system for cellular membranes to study the biochemistry of membrane proteins.85 Consequently, when liposomes were first tried as a drug delivery system, their bilayers were composed of un-derivatized naturally occurring lipids. Most of such conventional liposomes are taken up by the MPS phagocytes within a few hours of injection, mostly by liver Kupffer cells and spleen macrophages.9 Inside the endosomes and lysosomes of those cells, liposomes are degraded. If the liposomal drugs are membrane permeable, they then can diffuse from the endosomal compartments to the cytoplasm of the macrophage cells and slowly reenter the blood circulation. Because such a clearance... 

Liu et al. [7] found significant differences between the disposition of complexed and uncomplexed [1251]-labeled plasmid DNA in mice. An equal amount of radioactivity was found in blood and liver at 15 min after injection of naked plasmid DNA. In contrast, at the same time-point, a major portion of injected DNA was in the lung when DNA-lipid complexes were injected. 

Effects on blood lipids are complex and variable, and the balance may be to disadvantage. 

A variety of lipid-protein complexes are used in the body to transport relatively water-insoluble lipids, such as triglycerides and cholesterol, in circulating blood. These complexes are commonly called lipoproteins they contain both proteins and lipids in varying concentrations. The density of these lipoproteins depends on the relative amounts of protein, because lipids are less dense than protein. Low density lipoproteins, or LDLs, have a relatively higher ratio of lipid to protein. LDLs are used to transport cholesterol and triglycerides from the liver to the tissues. In contrast, high density... 

The lipids are among the most important components of human diet and occur widely in nature. However, it is the biochemical role of lipids as the basic components of various cellular membranes and the lipid-protein complexes (lipoproteins) that bring them into the focus of highly important scientific activities. Major clinical interest has concentrated on blood lipid chemistry as related to atherosclerosis, lipid storage diseases, diabetes, and other metabolic conditions. 

Introduction - Atherosclerosis is defined by the WHO "as a variable combination of changes of the intima of arteries consisting of the focal accvimulation of lipids, complex carbohydrates, blood and blood products, fibrous tissue and calcium deposits and associated with medial changes." Once formed the advanced plaque seldom regresses, and consequently major research attention has concentrated on prevention of additional deposits or, in the longer view, on the primary prevention of all lesions. 

When most lipids circulate in the body, they do so in the form of lipoprotein complexes. Simple, unesterified fatty acids are merely bound to serum albumin and other proteins in blood plasma, but phospholipids, triacylglycerols, cholesterol, and cholesterol esters are all transported in the form of lipoproteins. At various sites in the body, lipoproteins interact with specific receptors and enzymes that transfer or modify their lipid cargoes. It is now customary to classify lipoproteins according to their densities (Table 25.1). The densities are... 

The Jing group investigated their poly(L-lysine)-6-poly(L-phenylalanine) vesicles for the development of synthetic blood, since PEG-lipid vesicles were previously used to encapsulate hemoglobin to protect it from oxidation and to increase circulation time. They extended this concept and demonstrated that functional hemoglobin could be encapsulated into their vesicles. The same polypeptide material was also used to complex DNA, which caused the vesicles to lose their... 

Glycosphingolipids (GSLs) (neutral GSLs, gangliosides, and complex species, including the ABO blood group substances) constitute about 5-10% of the total lipid. 

In contrast, the carotenes such as p-carotene and lycopene may position themselves parallel to the membrane surfaces to remain in a more lipophilic environment in the inner cores of the bilayer membranes. To move through an aqueous environment, carotenoids can be incorporated into lipid particles such as mixed micelles in the gut lumen or lipoproteins in the blood circulation and they can also form complexes with proteins with unspecific or specific bindings. 

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). 

Thus, the mechanism of MT antioxidant activity might be connected with the possible antioxidant effect of zinc. Zinc is a nontransition metal and therefore, its participation in redox processes is not really expected. The simplest mechanism of zinc antioxidant activity is the competition with transition metal ions capable of initiating free radical-mediated processes. For example, it has recently been shown [342] that zinc inhibited copper- and iron-initiated liposomal peroxidation but had no effect on peroxidative processes initiated by free radicals and peroxynitrite. These findings contradict the earlier results obtained by Coassin et al. [343] who found no inhibitory effects of zinc on microsomal lipid peroxidation in contrast to the inhibitory effects of manganese and cobalt. Yeomans et al. [344] showed that the zinc-histidine complex is able to inhibit copper-induced LDL oxidation, but the antioxidant effect of this complex obviously depended on histidine and not zinc because zinc sulfate was ineffective. We proposed another mode of possible antioxidant effect of zinc [345], It has been found that Zn and Mg aspartates inhibited oxygen radical production by xanthine oxidase, NADPH oxidase, and human blood leukocytes. The antioxidant effect of these salts supposedly was a consequence of the acceleration of spontaneous superoxide dismutation due to increasing medium acidity. 

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