Liposome lipid components

When liposomes are prepared from a molecular mixture of lipid components it is important that all lipids be homogeneously dissolved in an organic solvent in order to obteiin bilayers with evenly distributed lipids after hydration. For example, the solubilities of phosphatidylcholine and cholesterol in chloroform are similar their solubility in benzene differs. Upon removal of benzene from the lipid solution an inhomogeneous lipid film is formed on the glass wall and... 

Other potential adverse effects resulting from liposome administration which need to be studied are undesired complement activation (Cunningham et al., 1979), blood clotting, and pharmacological effects of the lipid components as well as physical obstruction of small capillaries by large particles. 

For a number of liposome preparations—both injectables and locally administered products—the therapeutic advantages over existing formulations have been proven in animal models clinical trials with liposome preparations are now under way. So far, clinical studies showed no significant toxic effects which could be ascribed to the lipid components of the liposomes used. 

The determination of partition coefficients using liposomes as a lipid phase require that the sample be equilibrated with a suspension of liposomes, followed by a separation procedure, before the sample is quantitated in the fraction free of the lipid component. 

Once the desired mixture of lipid components is dissolved and homogenized in organic solvent, one of several techniques may be used to disperse the liposomes in aqueous solution. These methods may be broadly classified as (1) mechanical dispersion, (2) detergent-assisted solubilization, and (3) solvent-mediated dispersion. 

Two approaches for the activation of lipid components may be used to create reactive groups in liposomes. A purified lipid may be activated prior to incorporation into the bilayer construction... 

Liposomes containing PE lipid components may be activated with these crosslinkers to contain iodoacetyl derivatives on their surface (Figure 22.29). The reaction conditions described in Chapter 5, Section 1.5 may be used, substituting a liposome suspension for the initial protein being modified in that protocol. The derivatives are stable enough in aqueous solution to allow purification of the modified vesicles from excess reagent (by dialysis or gel filtration) without... 

Lipid components of liposomes must perform a number of functions. First, it is important that the DNA is packaged into a small particle to protect the DNA and condense it into a smaller particle compatible with cellular uptake. Next, the lipids must enable the transfection process, which involves three key stages cell attachment and uptake into the cell, endoso-mal escape, and then movement into the nucleus for the expression of the transferred gene (Fig. 1) (14). 

Two approaches for the activation of lipid components may be used to create reactive groups in liposomes. A purified lipid component may be activated prior to incorporation into the bilayer construction or the activation step may occur after formation of the intact liposome. Either way, the goal of the activation process is to provide a reactive species that can be used to couple with selected target functional groups on... 

Anderson, M., and A. Omri. 2004. The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations. Drug Deliv 11 33. 

AVE stands for artificial viral envelope [17]. In fact, the lipid components of the AVE liposomes are similar to the HIV envelope and mimic the red blood cell membrane [17]. HVJ-AVE liposomes gave gene expression in liver and muscle that was 5 to 10 times greater than observed with conventional HVJ liposomes [16]. HVJ-AVE liposomes were effective for gene delivery to isolated rat heart by way of the coronary artery. LacZ gene expression was observed in the entire heart, whereas no expression was observed with empty HVJ-AVE liposomes. 

Bilayer composition can be almost infinitely varied by choice of the constituent lipids. Phosphatidylcholine (PC), a neutral phospholipid, has emerged as the major lipid component used in the preparation of pharmaceutical liposomes. Phosphatidylglycerol and phosphatidylethanolamine are also widely used. Liposomal bilayers may also accommodate sterols, glycolipids, organic acids and bases, hydrophilic polymers, antibodies and other agents, depending on the type of vesicle required. 

Cationic liposomes are a relatively new development in liposomal therapeutics, which demonstrate considerable potential for improving the delivery of genetic material. The cationic lipid components of the liposomes interact with, and neutralize, negatively charged DNA, thereby condensing the DNA into a more compact structure. Depending on the preparation method used, the complex may not be a simple aggregate, but an intricate structure in which the condensed DNA is surrounded by a lipid bilayer. These systems are discussed further in Chapter 14. 

Kirby, C., and Gregoriadis, G. (1980), The effect of the cholesterol content of small unillamellar liposomes on the fate of their lipid components in vivo, Life Sci., 27, 2223-2230. 

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