Large unilamellar vesicle from multilamellar vesicles

Liposomes were first proposed for drug topical administration to the skin more than 25 years ago by Mezei and Gulusekharam [1,2]. The basic components of liposomes are phospholipids (phosphatidylcholine, phophatidylethanolamine, phophatidylserine, dipalmitoyl phosphatidylcholine, and others), cholesterol, and water. Liposomes may vary significantly in terms of size (from tens of nm to microns) and structure. In liposomes, one or more concentric bilayers surround an aqueous core generating small or large unilamellar vesicles (SUV, LUV) or multilamellar vesicles (MLV), respectively [3]. 

Liposomes used for transfection are either large unilamellar vesicles (LUVs) of 100 to 200 nm in diameter or small unilamellar vesicles (SUVs) of 20 to 100 nm. Liu et al.124 have reported that for a given liposome composition, multilamellar vesicles (MLVs) of 300 to 700 nm in diameter exhibit higher transfection efficiency than SUVs. However, more recent studies on the nature of the liposome-DNA complex (or lipoplex) revealed that lipoplexes from SUVs or MLVs do not differ significantly in size. On the other hand, the composition of the medium, not the type of the liposome used in the preparation of the lipoplex, plays a key role in determining the final size of the complex. And the transfection efficiency is also shown to depend on the final size of the complexes but not the type of the liposome.125... 

Figure 181. Effect of membrane components on the leakage of 5-fluorouracil from liposomes during storage at 4°C. O, LW (PC/PS/CH 7 4 5) A, LUV (MC/PS/CH 7 4 5) O, MLV (PC/PS/CH 7 4 5). LW, Large unilamellar vesicle, PC, l,2-dipalmitoyl-sn-glycero-3-phosphocholine monohydrate, PS, dipalmitoyl-DL-C phosphatidyl-L-serine, CH, cholesterol, MC, l,2-dimyristoyl-sn-glycero-3-phosphocholine monohydrate, MLV, multilamellar vesicle. (Reproduced from Ref. 717 with permission.)...

Suv, small unilamellare vesicles luv, large unilamellare vesicles mlv, multilamellare vesicles mvv, multivesiculare vesicles (Fig. 4 from [1.34]). 

In model systems for bilayers, one typically considers systems which are composed of one type of phospholipid. In these systems, vesicles very often are observed. The size of vesicles may depend on their preparation history, and can vary from approximately 50 nm (small unilamellar vesicles or SUVs) up to many pm (large unilamellar or LUV). Also one may find multilamellar vesicular structures with more, and often many more than, one bilayer separating the inside from the outside. Indeed, usually it is necessary to follow special recipes to obtain unilamellar vesicles. A systematic way to produce such vesicles is to expose the systems to a series of freeze-thaw cycles [20]. In this process, the vesicles are repeatedly broken into fragments when they are deeply frozen to liquid nitrogen temperatures, but reseal to closed vesicles upon thawing. This procedure helps the equilibration process and, because well-defined vesicles form, it is now believed that such vesicles represent (close to) equilibrium structures. If this is the case then we need to understand the physics of thermodynamically stable vesicles. 

There are several other ways to entrap solutes inside the liposomes, and the entrapping efficiency depends on the structure of liposomes (small unilamellar, large unilamellar, multilamellar, vesicles, etc.) and from the technique for liposome preparation (Roseman etal., 1978 Cullis etal., 1987 Walde and Ishikawa, 2001). 

Shapes of vesicular aggregates range from tubular to spherical, from more exotic large compound (LCV) and starfish vesicles to simpler extended lamellae. Both unilamellar [75] and multilamellar ( onions ) [47,76] vesicles have been observed. One of the possible morphologies formed in solution are tubular vesicles, also known as tubes (rods) [77,78], Soft, water-filled polymer tubes of nanometer-range diameters and several tens of millimeters in length have been prepared via self-assembly of amphiphilic ABA triblock copolymer in aqueous media (Fig. 4). The tubes were mechanically and chemically stable and could be loaded with water-soluble substances [23],... 

According to the preparation method chosen, several types of vesicle can be obtained, which differ in their size, their structure, and their capacity to encapsulate. Multilamellar vesicles (MLVs) have an average diameter varying from 400 nm to several micrometers, while unilamellar vesicles can have a large (80 nm to 1 pm LUV) or small (20-80 nm SUV) size [102]. 

The solubility of the monomers of bilayer-forming molecules is usually very low, say, in the range of 10 -10 ° M. Crystals of such amphiphiles immersed in water tend to swell. In this way lamellar liquid crystals (multilamellar vesicles) made up of bilayers packed in large stacks, separated by water molecules, are usually formed. They reach dimensions of a few thousands of nanometers. These lamellar structures may appear in different forms that readily interchange in response to small variations in temperature or composition. Unilamellar vesicles having a radius of a few tens up to a few hundreds of nanometers are derived from the lamellar liquid crystals by mechanical rupturing as occurs in ultrasonic treatment, for example. The unilamellar vesicles are thermodynamically unstable, and, hence, the properties of a unilamellar vesicle dispersion depend on how it was prepared. The colloidal stability of such a vesicle system is determined by the rate of fusion between two vesicles. This rate, in turn, is governed by the rules of colloidal stability discussed in Chapter 16. Anyway, the colloidal stability of unilamellar vesicles allows their use for in vitro studies of physical and chemical bilayer and membrane properties. 

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