MLVs

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 1 Effect of (sequential) extrusion of MLV dispersions through polycarbonate membrane filters (Unipore) with pore sizes of 1.0, 0.6, 0.4, 0.2, and 0.1 ym on the mean liposome diameter. DXR-containing MLV (phosphatidylcholine/phosphatidylserine/ cholesterol 10 1 4) mean diameter of nonextruded dispersion about 2 ym pH 4. Mean particle size determined by dynamic Light scattering (Nanosizer, Coulter Electronics). (From Crommelin and Storm, 1987.)... 

Some techniques to produce small, mainly unilamellar vesicles from MLV (sonication, French pressure cell) are discussed below in separate paragraphs. 

A method resulting in improved encapsulation of aqueous phase by MLV is the so-called dehydration-rehydration procedure (Kirby and Gregoriadis, 1984 Shew and Deamer, 1985). The lipid (usually preformed liposomes) is dried (by either lyophilization or evaporation) in the presence of the aqueous solute to be entrapped, thus forming a mixed film with solute trapped between layers. Subsequent gradual rehydration with a minimum of aqueous phase leads to the formation of MLV with a high entrapment of the aqueous solutes added. 

Reverse Phase Evaporation Szoka and Papahadjopoulos (1978) developed the so-called reverse phase evaporation method. Vesicles prepared with this technique (REV) show higher encapsulation efficiencies of hydrophilic compounds than unextruded MLV. 

Sonication of MLV dispersions above the Tc of the lipids results in the formation of SUV (Saunders, et al., 1962). Sonication can be performed with a bath sonicator (Papahadjopoulos and Watkins, 1967) or a probe sonicator (Huang, 1969). During sonication the MLV structure is broken down and small unilamellar vesicles with a high radius of curvature are formed. In case of SUV with diameters of about 20 nm (maximum radius of curvature), the outer monolayer can contain over 50% of the phospholipids and in the case of lipid... 

A French pressure cell can be used to reduce the size of MLV by extrusion under high pressure. Four extrusions of egg PC-MLV at 4°C resulted in the formation of small unilamellar vesicles 94% of the lipid was found in 31- to 52-nm vesicles (Barenholz et al., 1979). 

Size exclusion chromatography has been used to analyse the size distribution of liposomes. For example, SUV can be separated from MLV, which elute in the void volume, by using a Sepharose 4B gel. 

Several groups investigated the use of liposomes for the intra-pulmonary delivery. Farr et al. (1985) showed that the deposition of aerosolized liposomes in the human lung depends on the aerosol particle size. Short-term retention profiles for MLVs and SUVs deposited in the lung were indicative of clearance via the mucociliary transport mechanism. 

In comparison to intravenous administration of MLV, which usually results in a rapid and almost quantitative uptake into liver and spleen, the fraction taken up into these organs is lower after intraperitoneal injection of these large liposomes. The reason might be that liposomes are trapped in lymph nodes and degradation of the liposomes in the peritoneal cavity can occur (Ellens et al., 1981 Parker et al., 1982) besides, several types of liposomes are degraded more quickly in lymphatic fluid than in plasma (Parker et al, 1981a,b). 

MitcheU RS, Beitzel BF, Schroder AR, Shinn P, Chen H, Berry CC, Ecker JR, Bushman FD (2004) Retroviral DNA integration ASLV, HIV, and MLV show distinct target site preferences. PLoS Biol 2(8) E234... 

Liposomes — These are synthetic lipid vesicles consisting of one or more phospholipid bilayers they resemble cell membranes and can incorporate various active molecules. Liposomes are spherical, range in size from 0.1 to 500 pm, and are thermodynamically unstable. They are built from hydrated thin lipid films that become fluid and form spontaneously multilameUar vesicles (MLVs). Using soni-cation, freeze-thaw cycles, or mechanical energy (extrusion), MLVs are converted to small unilamellar vesicles (SUVs) with diameters in the range of 15 to 50 nm. ... 

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... 

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... 

For partition studies, only SUV [385,386] or LUV [149] should be used MLVs have many layers of trapped solution, which usually cause hysteresis effects [162],... 

Entry Catalyst /composition Surface area /mV1 Pore Volume /mLV Pore Diameter /nm Lattice Constant /nm Bulk Cone. /mol% Average Activity8 /% Selectivityb /%... 

Figure 10.11 Liposome structures, including multilamellar vesicles (MLV) and large unilamellar...

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