Lipids mechanical dispersion

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. 

Probably the most popular option is mechanical dispersion, simply because the greatest number of methods that utilize it have been developed. When using mechanical means to form vesicles, the lipid solution first is dried to remove all traces of organic solvent prior to dispersion in an aqueous media. The dispersion process is the key to... 

Based on the modes of lipid dispersion, the methods of liposomes formation can be classified into three categories mechanical dispersion, solvent dispersion, and detergent solubilization (175). These generally involve the following stages as evident in Figure 8.23. 

In mechanical dispersion, the lipids are dried down onto a solid support from organic solvents, followed by the dispersion of liposomes by adding the aqueous media through shaking. Other methods using mechanical dispersion techniques include freeze drying, pro-liposome preparation, hand shaking, and the non-shaken method (175). 

At higher temperatures, the protein moiety of hpoproteins undergoes denaturation (Anton et al., 2000), which affects the structure and the surface properties. Lipids and phospholipids are liberated from their complexes with proteins so that they become better available for further reactions (e.g., extraction or oxidation), hi technological and cuhnary operations, fats and oils or their emulsions are often added to the material, they are mechanically dispersed, and hydrogen bonds between hpid and protein molecules are formed or rearranged. Other weak physical forces also play a role. The final effect depends on the particular technology employed and the composition of the food. 

The production of CLS by the melt dispersion technique is based on the melting of the lipid core material together with the lipophilic agent (i.e., phospholipids). Afterward, a warm aqueous solution is added to the molten material and is mixed by various methods (i.e., mechanical stirring, shaking, sonication, homogenization). Then the preparation is rapidly cooled until lipid solidification and the formation of particle dispersion. This method was used by Olbrich et al. [19] to produce the cationic solid lipid nanoparticles to use as novel transfection agent. 

The solvent evaporation method resulted in the production of LS characterized by a smaller size (20 pm mean diameter) but poor mechanical properties in respect to particles with the same composition that were obtained by the melt dispersion technique (170 pm mean diameter). The use of a combination of lipids and a methacrylic polymer (Eudragit RSI00) overcame this problem, resulting in the production of spherical particles with a narrower size distribution and good mechanical properties [53,56],... 

Other surface-active compounds self-assemble into bilayer structures (schematically illustrated in Fig. 10b), which normally spherilize into structures termed vesicles. When vesicles are formed from phospholipids, the term liposome is used to identify the structures, which also provide useful drug delivery systems [71]. Solutes may be dispersed into the lipid bilayer or into the aqueous interior, to be subsequently delivered through a variety of mechanisms. Liposomes have shown particular promise in their ability to act as modifiers for sustained or controlled release. 

The mechanism of prooxidant effect of a-tocopherol in aqueous lipid dispersions such as LDLs has been studied [22], This so-called tocopherol-mediated peroxidation is considered in detail in Chapter 25, however, in this chapter we should like to return once more to the question of possible prooxidant activity of vitamin E. The antioxidant effect of a-tocopherol on lipid peroxidation including LDL oxidation is well established in both in vitro and in vivo systems (see, for example, Refs. [3,4] and many other references throughout this book). However, Ingold et al. [22] suggested that despite its undoubted high antioxidant efficiency in homogenous solution a-tocopherol can become a chain transfer agent in aqueous LDL... 

Perhaps the simplest solvent dispersion method is that developed by Batzri and Korn (1973). Phospholipids and other lipids to be a part of the liposomal membrane are first dissolved in ethanol. This ethanolic solution is then rapidly injected into an aqueous solution of 0.16 M KC1 using a Hamilton syringe, resulting in a maximum concentration of no more than 7.5% ethanol. Using this method, single bilayer liposomes of about 25-nm diameter can be created that are indistinguishable from those formed by mechanical sonication techniques. The main disadvantages of ethanolic injection are the limited solubility of some lipids in the solvent (about 40 mM for phosphatidyl choline) and the dilute nature of the resultant liposome suspension. However, for the preparation of small quantities of SUVs, this method may be one of the best available. 

T. Ogiso, N. Niinaka, and M. Iwaki. Mechanism for enhancement effect of lipid disperse system on percutaneous absorption, J. Pharm. Sci. 6 5 57-64 (1996). 

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 molecular mechanism of local anesthesia, the location of the local anesthetic dibucaine in model membranes, and the interaction of dibucaine with a Na+-channel inactivation gate peptide have been studied in detail by 2H- and 1H-NMR spectroscopy [24]. Model membranes consisted of PC, PS, and PE. Dibucaine was deuterated at H9 and H3 of the butoxy group and at the 3-position of the quinoline ring. 2H-NMR spectra of the multilamellar dispersions of the lipid mixtures were obtained. In addition, spectra of deuterated palmitic acids incorporated into mixtures containing cholesterol were obtained and the order parameter, SCD, for each carbon... 

Instability of an emulsion may be physical or chemical in nature. Chemical instability, which results in an alteration in the chemical structure of the lipid molecules due to oxidation or hydrolysis (McClements, 1999), will not be considered in this chapter for more information, the reader is referred to Chapters 11 and 12. Physical instability results in an alteration in the spatial distribution or structural organization of the globules (i.e., the dispersed phase of the emulsion). A number of important mechanisms responsible for the physical instability of emulsions, as depicted in Figure 5.1, can be divided into two categories gravitational separation and droplet aggregation. 

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