Constituents of Liposomes

Phospholipids are the most important of these liposomal constituents. Being the major component of cell membranes, phospholipids are composed of a hydrophobic, fatty acid tail, and a hydrophilic head group. The amphipathic nature of these molecules is the primary force that drives the spontaneous formation of bilayers in aqueous solution and holds the vesicles together. 

Naturally occurring phospholipids can be isolated from a variety of sources. One of the most common phospholipid raw materials is egg yolk. However, since the composition of egg phospholipid is from a biological source and can vary considerably depending on age of the eggs, the diet of the chickens, and the method of processing, newer enzymatic and synthetic chemical methods now are being employed to manufacture the required phospholipid derivatives in higher purity and yield. 

The fatty acid constituents of phosphodiglycerides can vary considerably in nature among a number of different chain lengths and points of unsaturation. A given isolated phosphatidyl 

By contrast, a given synthetic preparation of a major phospholipid possesses fatty acid constituents all of identical chain length and unsaturation. A synthetic PC derivative can be purchased that contains only, for instance, 1,2-dimyristoyl (C14) fatty acid substitutions on its glyceryl 

The nomenclature for associating individual fatty acid groups with particular phosphodig-lyceride derivatives is straightforward. For instance, a phosphatidic acid (PA) derivative which contains two myristic acid chains is commonly called dimyristoyl phosphatidic acid (DMPA). Likewise, a PC derivative containing two palmitate chains is called dipalmitoyl phosphatidyl choline (DPPC). Other phosphodiglyceride derivatives are similarly named. 

Naturally occurring phospholipids can be isolated from a variety of sources. One of the most common phospholipid raw materials is egg yolk. However, since the composition of egg phosphohpid is from a biological source and can vary considerably 

Despite the large variety of potential fatty acid components in natural-occurring phosphodiglycerides, only three major fatty acid derivatives of synthetic phospholipids are commonly used in liposome preparation (1) myristic acid (w-tetradecanoic acid containing 14 carbons), (2) palmitic acid (w-hexadecanoic acid containing 16 carbons), and (3) stearic acid (w-octadecanoic acid containing 18 carbons) (Fig. 334). 

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Liposomes are artificial structures primarily composed of phospholipid bilayers exhibiting amphiphilic properties. Other molecules, such as cholesterol or fatty acids also may be included in the bilayer construction. In complex liposome morphologies, concentric spheres or sheets of lipid bilayers are usually separated by aqueous regions that are sequestered or compartmentalized from the surrounding solution. The phospholipid constituents of liposomes consist of hydrophobic lipid tails connected to a head constructed of various glycerylphosphate... 

Presently, several clinical trials with liposome-encapsulated agents are under way and more are planned (Zonneveld and Crommelin, 1988 Klausner, 1988). During the last 5 years, key issues related to the pharmaceutical manufacturing of liposomes such as stability, sterilization, upscaling, and reproducibility have been successfully addressed. Although it is generally believed that a proper selection of the bi-layer components can minimize the occurrence of toxic effects due to the use of natural body constituents, the issue of liposome-related toxicity is not a trivial one and should be carefully studied,... 

Liposomes represent an important class of carrier vehicles other than polymers for drug delivery. This paper provides an introduction and general review of liposomes with emphasis on their classifications, their constituent materials, their preparation and characterizaton, and their stability and biodistribution in the body. Liposomes with specific characteristics are also described in this general introduction. 

Palmitic acid is conjugated to glucuronic acid to form a reticuloendothelial system-avoiding liposome delivery system (79). Phospholipids such as phosphatidyl choline or phosphatidyl ethanolamine are used as constituents of lipid complexes or... 

Principles to stabilize lipid bilayers by polymerization have been outlined schematically in Fig. 4a-d. Mother Nature — unfamiliar with the radically initiated polymerization of unsaturated compounds — uses other methods to-stabilize biomembranes. Polypeptides and polysaccharide derivatives act as a type of net which supports the biomembrane. Typical examples are spectrin, located at the inner surface of the erythrocyte membrane, clathrin, which is the major constituent of the coat structure in coated vesicles, and murein (peptidoglycan) a macromolecule coating the bacterial membrane as a component of the cell wall. Is it possible to mimic Nature and stabilize synthetic lipid bilayers by coating the liposome with a polymeric network without any covalent linkage between the vesicle and the polymer One can imagine different ways for the coating of liposomes with a polymer. This is illustrated below in Fig. 53. 

In a more recent study, vesicle skin interactions were examined with confo-cal laser scanning microscopy (CLSM) [36], A large number of liposome compositions were examined. These studies revealed that the liposome constituents were only present in the outermost layers of the SC and that the constituents only acted as penetration enhancers, which is in contrast to the studies of Holland et al. Whether these differences in findings are due to another study design or to a difference in vesicle components is not clear. 

Bioactive films made by the LbL technique have been extensively studied by many scientific groups worldwide. The films can host not only bioactive molecules introduced as constituents of the film, but also carriers with encapsulated biomolecules, for instance liposomes (Lip) and polymeric capsules (Fig. 2). Stimuli-sensitive... 

Cholesterol is a basic constituent of cell membranes and is known to affect their properties [10]. Thus experiments with liposomes incorporating varying amounts of cholesterol may simulate the function of cholesterol in cell mem-... 

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