Multilamellar

In water, a particle of lecithin exhibits myelin growth, ie, cylindrical sheets that are formed by bdayers and are separated by water which may break up into liposomes (vesicles with a single bilayer of Hpid enclosing an aqueous space). PhosphoHpids more generally form multilamellar vesicles (MLV) (5). These usually are converted to unilamellar vesicles (ULV) upon treatment, eg, sonication. Like other antipolar, surface-active agents, the phosphoHpids are... 

Figure 2 Snapshot from an MD simulation of a multilamellar liquid crystalline phase DPPC bilayer. Water molecules are colored white, lipid polar groups gray, and lipid hydrocarbon chains black. The central simulation cell containing 64 DPPC and 1792 water molecules, outlined m the upper left portion of the figure, is shown along with seven replicas generated by the periodic boundary conditions. (From Ref. 55.)...

In the typical setup, the lipids are arranged in a bilayer, with water molecules on both sides, in a central simulation cell, or box, which is then replicated by using three-dimensional periodic boundary conditions to produce an infinite multilamellar system (Fig. 2). It is important to note that the size of the central cell places an upper bound on the wavelength of fluctuations that can be supported by the system. 

Phospholipids e.g. form spontaneously multilamellar concentric bilayer vesicles73 > if they are suspended e.g. by a mixer in an excess of aqueous solution. In the multilamellar vesicles lipid bilayers are separated by layers of the aqueous medium 74-78) which are involved in stabilizing the liposomes. By sonification they are dispersed to unilamellar liposomes with an outer diameter of 250-300 A and an internal one of 150-200 A. Therefore the aqueous phase within the liposome is separated by a bimolecular lipid layer with a thickness of 50 A. Liposomes are used as models for biological membranes and as drug carriers. 

Multilamellar liposomes, absorbed on paper, containing extrapped peroxidase permit the quantitative determination of alcohol sulfates by measuring the amount of peroxidase released from the liposomes as this amount varies with the amount of surfactant [272]. 

Liposomes are members of a family of vesicular structures which can vary widely in their physicochemical properties. Basically, a liposome is built of one or more lipid bilayers surrounding an aqueous core. The backbone of the bilayer consists of phospholipids the major phospholipid is usually phosphatidylcholine (PC), a neutral lipid. Size, number of bilayers, bilayer charge, and bilayer rigidity are critical parameters controlling the fate of liposomes in vitro and in vivo. Dependent on the preparation procedure unilamellar or multilamellar vesicles can be produced. The diameter of these vesicles can range from 25 nm up to 50 ym—a 2000-fold size difference. 

Formation from Template Surfaces Recently, a new method for the preparation of LUV was reported by Lasic et al. (1988). The method is based on a simple procedure which leads to the formation of homogeneous populations of LUV with a diameter of around L vim. Upon addition of solvent to a dry phospholipid film deposited on a template surface, vesicles are formed instantly without any chemical or physical treatment. The formation of multilamellar structures is prevented by inducing a surface charge on the bilayers. The size of the vesicles is controlled by the topography of the template surface on which the phospholipid film was deposited (Lasic, 1988). 

Subcutaneous injection of insulin encapsulated in liposomes in rats resulted in prolonged hypoglycemic effects compared to a solution of free insulin this study also indicated that a substantial fraction of hand-shaken multilamellar vesicles could enter the circulation in intact form after subcutaneous injection (Stevenson et al., 1982). The neutral liposomes used in this study were cleared more slowly from the injection site than the negatively charged liposomes. 

Grliner, S. M., Lenk, R. P., Janoff, A. S., and Ostro, M. J. (1985). Novel multilayered lipid vesicles Comparison of physical characteristics of multilamellar liposomes and stable plurilamellar vesicles, Biochemistry. 24. 2833-2842. 

H. E., and Crommelin, D. J. A., Characterization of liposomes (1987). The influence of extrusion of multilamellar vesicles through polycarbonate membranes on particle size, particle size distribution and number of bilayers, Int. J. Pharm.. 35, 263-274. 

Mayer, L. D., Hope, M. J., Cullis, P. R., and Janoff, A. S. (1985a). Solute distributions and trapping efficiencies observed in freeze-thawed multilamellar vesicles, Biochim. Biophys. Acta, 817, 193-196. 

Perez-Soler, R., Lopez-Berestein, G., Kasi, L. P., Cabanillas, F., Jahns, M., Glenn, H., Hersh, E. M., and Haynie, T. (1985). Distribution of technetium labeled multilamellar liposomes in patients with Hodgkin s disease, J. Nucl. Med., 26, 743-749. 

Perez-Soler, R., Khokhar, A. R., Hacker, M. P., and Lopez-Berestein, G. (1986). Toxicity and antitumor activity of cis-bis-cyclopentenecarboxylato-1,2-diaminocyclohexane platinum(II) encapsulated in multilamellar vesicles. Cancer Res., 46. 6269-6273. 

There has been considerable discussion regarding the mode of action of the sea cucumber and starfish saponins. Both the triterpene and steroidal glycosides inhibit both Na/K ATPase and Ca/Mg ATPase 06) possibly as a result of their aglycone structures. However, their detergent properties cause membrane disruption which will influence the activity of membrane-bound enzymes such as the ATPases. In investigating the actions of saponins on multilamellar liposomes, it was found that cholesterol serves as the binding site for such saponins and that cholesterol-free lip-somes are not lysed by saponins 107). 

The Ca -ATPase microcrystals formed in detergent-solubilized sarcoplasmic reticulum in the presence of 20 mM Ca " and 20% glycerol contain highly ordered crystalline sheets of Ca -ATPase molecules, that associate into multilamellar stacks (Fig. 6) consisting frequently of more than 100 layers [156,183-185]. 

Vesicles [10, 11] these aggregates of insoluble natural or artificial amphiphiles in water can have various shapes (spherical, cylindrical). Depending on the preparation conditions, small unilamellar or large multilamellar vesicles can be produced. The structures meet the self-organization criterion, because they are, albeit on a long time scale, dynamic and not in thermodynamic equilibrium, which would in many cases be a macroscopically phase separated lamellar phase. 

Fragata, M., Ohnishi, S., Asada, K., Ito, T. and Takahashi, M. (1984) Lateral diffusion of plastocyanin in multilamellar mixed-hpid bilayers studied by fluorescence recovery after photobleaching. Biochemistry, 23, 4044—4051. 

Liposomes are formed due to the amphiphilic character of lipids which assemble into bilayers by the force of hydrophobic interaction. Similar assemblies of lipids form microspheres when neutral lipids, such as triglycerides, are dispersed with phospholipids. Liposomes are conventionally classified into three groups by their morphology, i.e., multilamellar vesicle (MLV), small unilamellar vesicle (SUV), and large unilamellar vesicle (LUV). This classification of liposomes is useful when liposomes are used as models for biomembranes. However, when liposomes are used as capsules for drugs, size and homogeneity of the liposomes are more important than the number of lamellars in a liposome. Therefore, "sized" liposomes are preferred. These are prepared by extrusion through a polycarbonate... 

Figure 1. Structure of liposomes and lipid microsphere a), multilamellar vesicle b). unilamellar vesicle c). lipid microsphere. Symbols inside the microsphere indicate di- and tri-acyl glycerol.

Liposomes have been, and continue to be, of considerable interest in drug-delivery systems. A schematic diagram of their production is shown in Fig. 10. Liposomes are normally composed of phospholipids that spontaneously form multilamellar, concentric, bilayer vesicles, with layers of aqueous media separating the lipid layers. These systems, commonly referred to as multilamellar vesicles (MLVs), have diameters in the range of 15 pm. Sonication of MLVs... 

A method where phospholipids are entrapped in the pores of resin beads, in the forms of multilamellar vesicles, has been described [313-319,376]. In some ways, the idea is similar to that of IAM chromatography, even though the resin is modified differently. The retention indices correlate very well with the partition coefficients measured in liposome-water systems (described below). 

Multilamellar PC Polar head/bulk water Fluoresecence polarization (ANS) 32 447... 

Multilamellar PC Polar head/acyl core Fluorescence polarization (AWV -DOC) 25 447... 

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