Liposome forming lipids

When synthetic lipids are used, detergent removal has to be performed above the corresponding transition temperature T of the lipid. Hence, when for example dipalmitoylphosphatidyl choline (DPPC) is used as main liposome forming lipid, a temperature above its T of 4DC has to be chosen. Additional membrane forming components (cholesterol, lipophilic drugs, etc.) depress the T by several degrees. 

Table 1 Several examples of pol3mierizable, liposome-forming lipid analogues (cf. Fig. 1).

FIG. 15 Cellular entry and intracellular kinetics of the cationic lipid-DNA complexes. Cationic lipid-DOPE liposomes form electrostatic complexes with DNA, and, in this case, also transferrin (Tf) is incorporated. Cellular uptake by endoc5dosis and endosomal acidification can be blocked with cytochaiasin B and bafilomycin Aj, respectively. DNA is proposed to be released at the level of endosomal wall after fusion of the carrier lipids with endosomal bilayer. This process is facilitated by the formation of inverted hexagonal DOPE phase as illustrated in the lower corner on the right. After its release to the C5doplasm DNA may enter the nucleus. (From Ref. 253. By permission of Nature Publishing Group.)... 

FIGURE 2.3 Temperature dependency of the absorption spectra of zeaxanthin incorporated into the liposomes formed with DPPC. The initial concentration of zeaxanthin in the medium used to prepare liposomes was 5 mol% with respect to lipid. (Based on the results presented in Sujak, A. et al., Biochim. Biophys. Acta, 1509, 255, 2000.)... 

All of the above-mentioned examples describe organosiloxane hybrid sheet-like structures. However, cell-mimicry requires spherical structures that can form an inner space as a container. Liposomes and lipid bilayer vesicles are known as models of a spherical cell membrane, which is a direct mimic of a unicellular membrane. However, the limited mechanical stability of conventional lipid vesicles is often disadvantageous for some kinds of practical application. 

Many types of liposomes of different lipid composition and different sizes having a transmembrane AS gradient were prepared (10). These liposomes varied (i) in their liposome-forming phosphatidylcholine (PC), being with and without cholesterol and/or lipopolymer (ii) in their size and (iii) in their method of preparation. The approaches for preparing these different liposome formulations varies in their lipid hydration and downsizing. Table 1 in Haran et al. (10) gives a partial list of such liposome preparations. In all cases the scheme of liposome preparation can be summarized as described in Table 4. 

Studies of the reaction of ozone with simplified lipid systems have shown that malonaldehyde can be produced by direct ozonolysis. The use of malonaldehyde assay as an index of lipid peroxidation is therefore invalid in ozone studies. Liposomes formed from egg lecithin and prepared in aqueous media were quite resistant to ozone, but the contribution of polyconcentric spheres to this resistance has not been fully assessed. However, the bilayer configuration, with the susceptible unsaturated fatty acids shielded from ozone by the hydrophilic areas of the molecule, may be resistant. In hexane, where the fatty acid moieties are exposed, ozone reacts stoichiometrically with the double bonds. The experiments with aqueous suspensions of phosphatidylcholine gave no evidence of the formation of lipid peroxides,nor did experiments with films of fatty acids exposed to ozone. ... 

Most materials used to produce liposomes are derived from natural materials, thus are thought to be safe when administered. Generally, however, phospholipids administered in liposomal form are cleared from the lungs more slowly than comparable doses of lung surfactant (Oguchi et al. 1985). Many macromolecules have been incorporated into liposomes in order to improve their pulmonary delivery. Some lipid-entrapped macromolecules have been tested in animal models and human volunteers to determine efficacy (Kellaway and Farr 1990). 

Lu, F. S. H., Nielsen, N. S., Timm-Heinrich, M., and Jacobsen, C. (2011). Oxidation stability of marine phospholipids in the liposomal form and their applications. Lipids 46, 3-23. 

Biological membranes are constructed of lipid bilayers 3 nm (30 A) thick, with proteins protruding on each side. The hydrocarbon core of the membrane, made up of the —CH2— and —CH3 of the fatty acyl groups, is about as nonpolar as decane, and liposomes formed in the laboratory from pure lipids are essentially impermeable to polar solutes, as are biological membranes (although the latter, as we shall see, are permeable to solutes for which they have specific transporters). 

Hupfer, B., Rinsdorf, H., and Schupp, H. (1983). Liposomes form polymerizable lipidsm. Phys. Lipids,... 

The alternative to encapsulation of free manganese (called ensomes ) is to complex the manganese(II) with a ligand embedded in the lipid bilayer ( mem-somes ). Ethylenediaminetetraacetic acid (EDTA)-dihydroxypropyldecylamine (EDTA-DDP, Fig. 2) was ligated to manganese(II) and inserted into the bilayer of liposomes [61]. The 30-nm diameter liposomes formed had an R, value at 20 MHz of 37.4 mM"1 s1. When injected into rats with implanted C5 epitheloid... 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

It needs to be emphasized that the results from calcium channel antagonists cannot be generalized with respect to the relative order and degree of partitioning into octanol, liposomes, and native membranes. The partition coefficients, JCM, and Doct of dopamine antagonists in brain membranes and liposomes formed by the extracted lipids were also found to vary. In the case of these drugs, Doct was larger... 

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