Liposome from amphiphilic lipids

In the discussion above it has been shown that the lipid can been polymerized through UV irradiation of its aqueous suspension. The polymerization of the system improves the stability of the synthetic liposomes. Since there is an acetal linkage introduced between the polymer chain and the amphiphilic structure, this linkage can be slowly hydrolyzed in aqueous systems to separate the polymer chain from the lipid. 

PDA liposomes usually have lipids with two alkyl chains but liposomes can be formulated with a single or multiple alkyl chains in the lipids. The length and number of the lipid tails controls the self-assembly process of the amphiphiles in addition to the transition temperature from crystalline to liquid chain packing. It has also been observed that an increase in the size of the chains results in a red color upon polymerization. PDA polymers that have nonequivalent tails are 6500-fold less efficient at polymerization than those of the corresponding equivalent two-tailed monomers The increase in efficiency of two-tailed monomers is likely the result of better alignment for more optimal geometry. 

For some time, there has been interest in the controlled release properties of stabilized liposomes.(i-3) A number of methods for stabilizing liposomes have been developed. Liposomes have been prepared from lipids which contain polymerizable groups such as methacrylate, butadiyne, or diacetylene and subsequently polymerized.(4-6) Another strategy is to n e liposomes from lipids with amino add headgroups and then potymerize the liposome Ity potycondensatioiL(7) Alternatively, stabilized liposomes have been prepared from prepolymerized amphiphiles.(8) Recently, the design and preparation of... 

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

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... 

Liposomes and micelles are lipid vesicles composed of self-assembled amphiphilic molecules. Amphiphiles with nonpolar tails (i.e., hydrophobic chains) self-assemble into lipid bilayers, and when appropriate conditions are present, a spherical bilayer is formed. The nonpolar interior of the bilayer is shielded by the surface polar heads and an aqueous environment is contained in the interior of the sphere (Figure 10.3A). Micelles are small vesicles composed of a shell of lipid the interior of the micelle is the hydrophobic tails of the lipid molecules (Figure 10.3B). Liposomes have been the primary form of lipid-based delivery system because they contain an aqueous interior phase that can be loaded with biomacromolecules. The ability to prepare liposomes and micelles from compounds analogous to pulmonary surfactant is frequently quoted as a major advantage of liposomes over other colloidal carrier systems. 

As an example of an asymmetric membrane integrated protein, the ATP synthetase complex (ATPase from Rhodospirillum Rubrum) was incorporated in liposomes of the polymerizable sulfolipid (22)24). The protein consists of a hydrophobic membrane integrated part (F0) and a water soluble moiety (Ft) carrying the catalytic site of the enzyme. The isolated ATP synthetase complex is almost completely inactive. Activity is substantially increased in the presence of a variety of amphiphiles, such as natural phospholipids and detergents. The presence of a bilayer structure is not a necessary condition for enhanced activity. Using soybean lecithin or diacetylenic sulfolipid (22) the maximal enzymatic activity is obtained at 500 lipid molecules/enzyme molecule. With soybean lecithin, the ATPase activity is increased 8-fold compared to a 5-fold increase in the presence of (22). There is a remarkable difference in ATPase activity depending on the liposome preparation technique (Fig. 41). If ATPase is incorporated in-... 

As previously mentioned, the functionalization of the external surface of liposomes was achieved through the preparation of mixed liposomes. In this manner, the functional moieties at the external surface originate from the amphiphilic components, which were incorporated in these mixed liposomes. It was thus possible to monitor the reactivity of liposomes by changing the type and concentration of the incorporated recognizable lipid. 

Another type of self-assembly mode is based on looser molecular interactions, where one of the main binding forces comes from hydrophobic interactions in aqueous media. Amphiphihc molecules (amphiphiles) that have a hydrophihc part and a hydrophobic part form various assembhes in water and on water. The simplest example of this kind of assembly is a micelle, where amphiphiles seh-assemble in order to expose their hydrophilic part to water and shield the other part from water due to hydrophobic interactions. A similar mechanism also leads to the formation of other assembhes, such as hpid bilayers. These molecules form spherical assembhes and/or two-dimensional membranes that are composed of countless numbers of molecules. These assembhes are usually very flexible. When external signals are applied to them, they respond flexibly while maintaining their fundamental organization and shape. This research held was initiated by the work of Bangham in 1964. It was found that dispersions of hpid molecules extracted from cells in water spontaneously form cell-like assembhes (liposomes). In 1977, Kunitake and Okahata demonstrated the formation of similar assembhes from various arti-flcial amphiphiles. The latter finding showed that natural lipids and artificial amphiphiles are not fundamentally different. 

Lipid bilayers are formed by many amphiphilic molecules in the presence of water. Their interest derives not only from the fact that they are a major, if not the only, organizing principle of biological membranes (1), but also because they tend to form closed (usually) spherical structures (liposomes or lipid bilayer vesicles) in which inner and outer aqueous spaces are separated by the lipid bilayers (2) which thereby provides a means of encapsulation (3, 4). 

Vineland, NJ) or over-the-counter cosmetic creams promoted for improved hydration (L Oreal, Paris and Dior, Paris). More recently, parenteral liposome formulations of amphotericin B, doxorubicin, and dau-norubicin have been approved and marketed (ABELCET, Elan, the Liposome Co., Inc, Princeton, NJ AmBisome and DaunoXome, Nexstar/Fujisawa, Deerfield Park, IL Amphotec and Doxil, Sequus/ Alza, Menlo Park, CA), with others on the horizon for applications in photodynamic therapy. Although the vast majority of liposome preparations are constructed from phospholipids, other nonphospholipid materials can be used either alone or in mixtures to form bilayer arrays. One such example is Amphotec, which utilizes sodium cholesteryl sulfate as the primary lipid. Other liposome forming materials may include but are not limited to fatty-acid compositions, ionized fatty acids, or fatty acyl amino acids, longchain fatty alcohols plus surfactants, ionized lysophospholipids or combinations, non-ionic or ionic surfactants and amphiphiles, alkyl maltosides, a-tocopherol esters, cholesterol esters, polyoxyethylene alkyl ethers, sorbitan alkyl esters, and polymerized phospholipid compositions. ° ... 

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