Lipid dispersion

P. E. Luner, D. V. Kamp. Wetting behavior of bile salt-lipid dispersions and dissolution media patterned after intestinal fluids. J. Pharm. Sci. 2001,... 

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... 

Liposome Formation. The pioneering investigations of Bang-ham (5) have shown that thin films of natural phospholipids form bilayer assemblies if they are lyophilized in excess water by simple handshaking above the phase transition temperature. While this procedure results in the formation of large, multibilayered spherical structures, by ultrasonication of such lipid dispersions small unilamellar liposomes are formed (16), which are schematically shown in Figure 10. Additional metTiods for liposome preparation are described in a number of reviews (17,44,45,46). 

Leventis R, Silvius JR. Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim Biophys Acta 1990 1023(1) 124-132. 

To obtain more detailed information on the ultrastructure of lipid dispersions and the morphology of the particles, electron microscopy is usually performed on replicas of freeze fractured or on frozen hydrated samples. These techniques aim to preserve the liquid-like state of the sample and the organization of the dispersed structures during preparation. By using special devices, the sample is frozen so quickly that all liquid structures, including the dispersion medium, solidify in an amorphous state. 

Phospholipid vesicles form spontaneously when distilled water is swirled with dried phospholipids. This method of preparation results in a highly polydisperse array of multicompartment vesicles of various shapes. Extrusion through polymeric membranes decreases both the size and polydispersity of the vesicles. Ultrasonic agitation is the most widely used method for converting the lipid dispersion into single-compartment vesicles of small size. 

We have observed such a transition in intact membranes of M. laidlawii which occurs at the same temperature as in the membrane lipids dispersed in water (77). Figure 11 shows representative endothermic transitions of membranes and lipids in water. Membranes were prepared for calorimetry by sedimenting at high speed, then 90-100 mg. of packed pellet were sealed in a stainless steel sample pan. The material was neither dried nor frozen before examination. Total membrane lipids were extracted with chloroform-methanol 2 1 v/v then dried and suspended in water. Lipids from the membranes of cells grown in the usual tryptose medium without added fatty acids are shown in a, while b and c are scans of intact membranes from the same cells. In b the membrane preparation had not been previously exposed to temperatures above 27 °C. The smaller transition at higher temperature probably arises from... 

Figure 13. NMR spectra at 35°C. of (a) low density lipoprotein lipids dispersed in D20 by sonication, 512 grams phosphorus/ml. (b) low density serum lipoproteins in 0.1 M Nad-D O, 625 grams lipid phosphorus/ml. (c) high density serum lipoproteins in 0.1 M NaCl-D/0, 832 pgrams lipid phosphorus/ml. Spectrum for high density lipoprotein lipids dispersed in water by sonication was essentially identical to (a). Spinning side bands are labeled S...

Figure 16. NMR spectra of total mitochondrial phospholipids at 40° C. in D20 (a) 15 w/v% lipids dispersed without sonication, (b) 8 w/v% lipids dispersed by sonication...

Alternatively, nanosized drug delivery particles, such as lipid-based nanoparticles or the nano-structured lipid dispersions can be produced by dispersing water-insoluble drug in lipid-based... 

Fig. 25 (a) DNA release from EDOPC-DNA lipoplexes after addition of negatively charged lipid dispersion, as monitored by FRET (CM, oleic acid DOPA, dioleoyl phosphatidic acid DOPG, dioleoyl phosphatidylglycerol CL, cardiolipin DOPS, dioleoyl phosphatidylserine PI, phospha-tidylinositol). (b) Fraction of released DNA from EDOPC lipoplexes 10 min after addition of the respective anionic liposomes (c) X-ray diffraction patterns of mixtures of EDOPC and anionic liposome dispersions the respective structures are shown schematically on the left side (reproduced with permission from [98] copyright (2004) Biophysical Society)... 

In many cases the relatively complex nature of lipid-based formulations in terms of lipid class, chain length, degree of dispersion, and choice of surfactant makes explanation of the mechanistic information difficult. For example, the bioavailability of vitamin E after administration of vitamin E acetate is greater after administration in a medium-chain triglyceride (MCT)-based emulsion compared with a long-chain triglyceride (LCT)-based lipid solution however, the differential roles of lipid dispersion or lipid class (MCT vs. LCT) cannot be separated [37],... 

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). 

Thewalt, J. et al., Models of stratum corneum intercellular membranes the sphingolipid headgroup is a determinant of phase behaviour in mixed lipid dispersions, Biochem. Biophys. Res. Commun., 188, 1247, 1992. 

Only a small quantity of an amphiphilic lipid dispersed in water can form a monolayer (unless the water is spread as a very thin film), in which case the bulk of the lipid will form soluble micelles. Micelles can take a variety of forms, each satisfying the hydrophobic effect. Fig. 6-2 shows one such form, representing a spherical micelle, although ellipsoidal, diskoidal, and cylindrical variations are possible. 

One-Step Method The one-step method has been introduced by Talsma et al. [140], Lipid dispersions are hydrated at high temperatures in the presence of a steam of N2. Liposomes between 200 and 500 nm can be prepared with this approach. 

Solid lipids, emulsifiers, and water are generally the ingredients involved for manufacturing SLNs. The term lipids is used in a broader sense and includes triglycerides (e.g., stearin), partial glycerides (e.g., Imwitor), fatty acids (e.g., stearic acid), steroids (e.g., cholesterol), and waxes (e.g., cetyl palmitate). All categories of emulsifiers may be used to stabilize the lipid dispersion, and the combination of emulsifiers prevents particle agglomeration more efficiently. The choice of the emulsifier depends on the administration route and is more limited for parenteral administration. 

Unilamellar vesicles are usually formed from lipid dispersions with sonication. Thus the suspension is metastablc, and vesicles aggregate to form a multilamellar structure. The decay time of sonicated phosphatidylcholine vesicles, as measured by DLS, showed a bimodal distribution 50. The hydrodynamic radius estimated from the smaller decay time was consistent with the values obtained by other experimental techniques such as ultracentrifugation. 

Fig. 11) has shown that this species is similarly solid in the same temperature range (Fenske et al., 1994). Thus we have reason to believe that the entire lipid dispersion is involved in the formation of this very immobilized phase. 

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. 

Table 3 Examples of heating, cooling, and isothermal phase sequences in lipid dispersions (44)...

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