Membrane models liposomes

Cantrell et al. (2003) studied the quenching of 02 by several dietary carotenoids in dipalmitoyl phosphatidylcholine (DPPC) unilamellar liposomes. These workers used water soluble and lipid soluble 02 sensitizers so that a comparison of the efficiencies of quenching 02 generated within and outside the membrane model could be made. Perhaps surprisingly there was little difference in the efficiency of quenching in either situation. Typical results are presented in Table 14.3 (taken from Cantrell et al. (2003 and 2006)). 

Fig. 5 Membrane models for NMR structure analysis, (a) An isotropic detergent micelle (left) is compared to the dimensions of lipid bilayers (right), (b) Macroscopically oriented membrane samples can be prepared on solid support, as nanodiscs, or as magnetically oriented bicelles. (c) Nomenclature and variability of liposomes small (SUV, 20-40 nm), intermediate (IUV, 40-60 nm), large (LUV, 100-400 nm), and giant unilamellar vesicles (GUV, 1 pm) multi-lamellar (MLV), oligo-lamellar (OLV) and highly heterogeneous multi-oligo-lamellar vesicles (MOLV)...

In the previous chapters it has been shown that stable cell membrane models can be realized via polymerization of appropriate lipids in planar monolayers at the gas-water interface as well as in spherical vesicles. Moreover, initial experiments demonstrate that polymeric liposomes carrying sugar moieties on their surface can be recognized by lectins, which is a first approach for a successful targeting of stabilized vesicles being one of the preconditions of their use as specific drug carriers in vivo. 

Chatterjee SN, Agarwal S. Liposomes as membrane model for study of lipid peroxidation. Eree Radic Biol Med 1988 4 51. 

Cevc, G. (1992). Lipid properties as a basis for membrane modeling and rational liposome ddairps[Pg.410]

Fortunately, most of the perturbations that can occur in complex biological membranes upon interaction with drug molecules can be studied and simulated in vitro and quantified by available physicochemical techniques, using as a model artificial membranes (bilayers, liposomes), which are readily created. 

Findings on the interaction of chemicals with biological membranes or model liposomes and methods for studying such interactions are mainly published in journals of biophysics or biochemistry. Only a few papers are published in journals of medicinal chemistry or pharmaceutical sciences. Even monographs on medicinal chemistry often lack some detailed information on this subject. 

Surfactants having two alkyl chains can pack in a similar manner to the phospholipids (see Box 6.4 for examples). Vesicle formation by the dialkyldimethylammonium cationic surfactants has been studied extensively. As with liposomes, sonication of the turbid solution formed when the surfactant is dispersed in water leads ultimately to the formation of optically transparent solutions which may contain single-compartment vesicles. For example, sonication of dioctadecyldimethyl-ammonium chloride for 30 s gives a turbid solution containing bilayer vesicles of 250-450 nm diameter, while sonication for 15 min produces a clear solution containing monolayer vesicles of diameter 100-150 nm. The main use of such systems has been as membrane models rather than as drug delivery vehicles because of the toxicity of ionic surfactants. 

As an example of a membrane model, phospholipid monolayers with negative charge of different density were used. It had already been found ( ) and discussed O) that the physical and biological behavior of phospholipid monolayers at air-water interfaces and of suspensions of liposomes are comparable if the monolayer is in a condensed state. Two complementary methods of surface measurements (using radioactivity and electrochemical measurements), were used to investigate the adsorption and the dynamic properties of the adsorbed prothrombin on the phospholipid monolayers. Two different interfaces, air-water and mercury-water, were examined. In this review, the behavior of prothrombin at these interfaces, in the presence of phospholipid monolayers, is presented as compared with its behavior in the absence of phospholipids. An excess of lipid of different compositions of phos-phatidylserine (PS) and phosphatidylcholine (PC) was spread over an aqueous phase so as to form a condensed monolayer, then the proteins were inject underneath the monolayer in the presence or in the absence of Ca. The adsorption occurs in situ and under static conditions. The excess of lipid ensured a fully compressed monolayer in equilibrium with the collapsed excess lipid layers. The contribution of this excess of lipid to protein adsorption was negligible and there was no effect at all on the electrode measurements. 

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