Artificial Membranes, Liposome Preparation, and Properties

During recent decades, the use of artificial phospholipid membranes as a model for biological membranes has become the subject of intensive research. As discussed above, biological membranes are composed of complex mixtures of lipids, sterols, and proteins. Defined artificial membranes may therefore serve as simple models of membranes that have many striking similarities with biological membranes. A comparison of some important physicochemical properties of biological and artificial membranes is given in Table 1.8 [2]. 

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. 

The structural dependence of phospholipid solutions on water content is called lysotropic polymorphism. At a water content of up to 30% dipalmitoylphosphatidyl-choline (DPPC) forms lamellar phases consisting of superimposed bilayers. Increasing the water content results in heterogeneous dispersions formed by multilamellar structures, the so-called liposomes (see also Section 1.3.1). 

Because of the complex composition of fatty acyl chains, a large variety of different molecules is present within each class of phospholipid, but they have in common their amphipathic nature. The packing of phospholipids depends on the normalized chain length difference between the sn-1 and sn-2 acyl chain. In addition to the bilayer structure of non-interdigitated acyl chains, mixed interdigitated and partially and totally interdigitated bilayer structures exist. 

Liposome preparations have been shown to be suitable not only for studying special drug-membrane interaction effects in vitro but also for use as drug carriers. Various techniques have been developed and described to prepare homogeneous unil- 

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