Permeability liposomes

The photoinduction ion flux derives from the similarity of vesicle systems to the proton flux in halobacterium halobium cell envelopes in the bacteriorhodopsin photocycle [126]. Liposome permeability to glucose can similarly be induced by photoexdtation in vesicles containing polyacetylene or thiophene as ion mediators [127]. As in planar bilayers, the surface charge [128] of the vesicle and the chain length of the component surfactant [129] influence assodation between the donor-acceptor pairs, and hence the distance of separation of components inside and outside the vesicle walls. 

The lower relative position of the sucrose-impermeable liposomes compared with those in D results from a longer centrifuge spin (8 h vs. 3 h) with longer spins the upper band tends to drift slowly to lower positions, a possible reflection of nonspecific liposome permeability (105). ... 

It is interesting to note than the structural requirement for the maximal interaction between sterols and lecithin monolayers [196] and for sterol-mediated reduction of liposome permeability [179] are a 3j3-hydroxyl group, a planar sterol nucleus and an intact C17 sidechain, which is identical with the requirement for maximal polyene sterol interaction [101,146]. 

Key words Liposomes, permeability, tenside cyclodextrin complex. 

McRae, D.G., E. Yamamoto, and G.H.N. Towers The Mode of Action of Polyacetylene and Thiophene Photosensitizers on Liposome Permeability to Glucose. Biochim. Biophys. Acta 821, 488 (1985). 

In addition to the reports of uptake of intact small liposomes (SUV) by hepatocytes (Scherphof et al., 1983), there is some evidence of uptake of intravenously administered liposomes as intact structures by cells other than mononuclear phagocytes of the MPS. Recently, the integrity of the capillary endothelial barrier in several pathophysiological conditions was discussed (Bodor and Brewster, 1986). Several studies already indicated an increased capillary permeability during inflammation both in animals (Lopez-Berestein et al., 1984a) and in man (Morgan et al., 1985 Williams et al., 1987). 

Liposomes, which are lipid bilayer vesicles prepared from mixtures of lipids, also provide a useful tool for studying passive permeability of molecules through lipid. This system has, for example, been used to demonstrate the passive nature of the absorption mechanism of monocarboxylic acids [131]. Liposome partitioning of... 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

The logk obtained by MEKC, MEEKC and LEKC were also compared with membrane permeability reference data by Ornskov et al. [92]. An improved correlation was obtained in the order MEKC>MEEKC>LEKC. Thus, LEKC appears to provide experimental conditions that mimic more closely physiological membranes [93], However, liposomes and vesicles remain unstable and difficult to prepare reproducibly. Their use is then devoted to some parhcular applicahons. 

Ornskov, E.,. Gottfries, M. Erickson, S. Folestad. Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions./. Pharm. Pharmacol. 2005, 57, 435 2. 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

Effect of Cholesterol. Cholesterol inclusion into the lipid bilayers composed of DPPC or DSPC, eliminates apparent Tc and reduces permeability at and above the usual Tc. On the other hand, cholesterol inclusion increases packing of fluid bilayer composed of lipids with unsaturated fatty acyl chains. Since cholesterol rich liposomes are stable in plasma, cholesterol is commonly used as a liposomal component. 

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

Using liposomes made from phospholipids as models of membrane barriers, Chakrabarti and Deamer [417] characterized the permeabilities of several amino acids and simple ions. Phosphate, sodium and potassium ions displayed effective permeabilities 0.1-1.0 x 10 12 cm/s. Hydrophilic amino acids permeated membranes with coefficients 5.1-5.7 x 10 12 cm/s. More lipophilic amino acids indicated values of 250 -10 x 10-12 cm/s. The investigators proposed that the extremely low permeability rates observed for the polar molecules must be controlled by bilayer fluctuations and transient defects, rather than normal partitioning behavior and Born energy barriers. More recently, similar magnitude values of permeabilities were measured for a series of enkephalin peptides [418]. 

Our present topic is the relationship between permeability and lipophilicity (kinetics), whereas we just considered a concentration and lipophilicity model (thermodynamics). Kubinyi demonstrated, using numerous examples taken from the literature, that the kinetics model, where the thermodynamic partition coefficient is treated as a ratio of two reaction rates (forward and reverse), is equivalent to the equilibrium model [23], The liposome curve shape in Fig. 7.20 (dashed-dotted line) can also be the shape of a permeability-lipophilicity relation, as in Fig. 7.19d. 

The permeability coefficient of 2.6x 10 locm/s at 296 K measured by Deamer is sufficient to supply the enzyme in the liposomes with ADP. How could it be shown that RNA formation actually does take place in the vesicles The increase in the RNA synthesis was detected by observing the fluorescence inside the vesicles. In the interior of the liposomes, the reaction rate is only about 20% of that found for the free enzyme, which shows that the liposome envelope does limit the efficiency of the process. The fluorescence measurements were carried out with the help of ethidium bromide, a fluorescence dye often used in nucleic acid chemistry. 

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