Permeability of liposomal membranes

Muranushi N, Nakajima Y, Kinugawa M, et al. Mechanism for the inducement of the intestinal absorption of poorly absorbed drugs by mixed micelles. Part 2. Effect of the incorporation of various lipids on the permeability of liposomal membranes. Int J Pharm 1980 4 281-290. 

Research by P. Scrimin and U. Toneiiato et ai. showed that Zn " was an aiiosteric reguiator of liposomal membrane permeability induced by synthetic template-assembled tripodal polypeptides. Several copies of peptide sequences from the peptaibol family were connected to fr/s(2-aminoethyl)amine (TREN), which is a tripodal metal ion ligand. The resulting tripodal polypeptides were capable of modifying the permeability of liposomal membranes, and their activity was tunable upon metal ion coordination of the TREN subunit. The synthesis of the TREN-based template began with the Stephen reduction of 4-cyanomethylbenzoate followed by the reductive amination of the resulting aldehyde with TREN. 

Finally, the effect of different chemosensitizers on the permeability of liposomes loaded with the membrane-impermeable chromophore carboxyfluorescein (CF) was studied as a model for the assumed change in membrane permeability of a number... 

We can now consider some typical nutrient solutes like amino acids and phosphate. Such molecules are ionized, which means that they would not readily cross the permeability barrier of a lipid bilayer. Permeability coefficients of liposome membranes to phosphate and amino acids have been determined [46] and were found to be in the range of 10 11 -10 12 cm/s, similar to ionic solutes such as sodium and chloride ions. From these figures one can estimate that if a primitive microorganism depended on passive transport of phosphate across a lipid bilayer composed of a typical phospholipid, it would require several years to accumulate phosphate sufficient to double its DNA content or pass through one cell cycle. In contrast, a modern bacterial cell can reproduce in as short a time as 20 min. 

Scrimin, P., Tecilla, P., Tonellato, U., Veronese, A., Crisma, M., Formaggio, F., Toniolo, C. Zinc(ll) as an allosteric regulator of liposomal membrane permeability induced by synthetic template-assembled tripodal polypeptides. Chem.-Eur. J. 2002, 8, 2753-2763. 

Magotoshi M, Samir SA, Noriaki T (1983) Size and permeability of liposomes extruded through polycarbonate membranes. Int J Pharm 17 215-224... 

Since the effect of TSH on TPMP+ uptake precedes the effect of the hormone on adenylate cyclase activity,1 7 the possibility exists that a primary mode of action of each of these effectors is to alter electrochemical ion gradients across the cell membrane. This concept is attractive in that it would serve to explain certain other findings. Thus, hCG causes changes in adrenal cell ion transport which not only precede adenylate cyclase stimulation, but occur at concentrations of the effector which have minimal effects on cyclase activity 1 9 cholera toxin and its B protein induce alterations in the permeability of liposomes reconstituted with "receptor" ganglioside in the absence of adenylate cyclase.50 51... 

The bouquet (91), incorporated into a phospholipid membrane of liposomes, increases the permeability of the membrane to Na" and Li. The ion transfer proceeds via a cation-cation antiport mechanism which has been established by Na and Li NMR spectroscopy <92AG(E)1637>. The incorporation of the bouquet molecule into several vesicular systems has been monitored by numerous techniques (UV, NMR, and CD spectroscopies, differential scanning calorimetry). It was concluded that different modes of incorporation take place and that several orientations of the bouquet coexist in the membranes <93JCS(P2)ioii>. 

Figure 17.5 Experimental methods to delivery a second reactant Y inside a X-containing vesicle. (1) Free (passive) diffusion ofY from outside to vesicle inside. (2) Fusion between two or more vesicles. (3) Microinjection of Y inside a giant vesicle. (4) Keeping the vesicles at the phase transition temperature (or by thermal cycles around T ). The permeability of lipid membranes is generally maximal at T - (5) Adding detergents at sublytic concentration, so that the membrane permeability is increased (especially for small solutes) without dramatic changes of membrane integrity. (6) Incorporation of pore-forming compounds in liposomes (a-hemolysin, OmpF porin,. ..)...

The permeability of liposomes prepared from synthetic lecithin have provided useful data which help to explain functional changes in membranes in terms of an alteration in bilayer structure. For example, the rate of water permeation through liposomes decreases 10-fold, and the of permeation increases from about 9 to 26 kcal mol" below the transition temperature for the lipids (Block et al., 1975). Rates of permeation for electrolytes and nonelectrolytes were found to be maximum at, or near, the temperature of the transition where fluid- and solid-phase lipids coexist, and decreased in both the gel and fluid phases below and above this temperature (Block et al., 1976). Since the order-disorder transition of lipids is accompanied by a decrease in the area per molecule, it was postulated that pores developed in the bilayer at the transition temperature and that the number and lifetime of these pores was dependent upon the fatty acid chain length of the lipids (Block eta/., 1976). 

Secondly, we investigated the effect of coating with these polysaccharides on the barrier function of liposomal membrane. The spontaneous release of carboxyfluorescein (CF) encapsulated in the interior of liposomes as a function of time was investigated at 50.0 °C (Fig. 3). Coating the outer surface of liposomes with these polysaccharides brought about several fold decrease in the permeability for CF. The substitution degree of acyl residues to behave as an anchor rather than the molecular weight of polysaccharide seems more important to coat conveniently the surface of liposomes. 

The permeability of polymersome membranes for a given solute has been reported to be at least 10 times smaller compared to common phosphohpid membranes (8). Retention of encapsulants (eg dextrans, sucrose, physiological saline) over periods of months has been observed for small 100 nm polymersomes prepared by liposome-type extrusion techniques (49) as well as with 10 p.m giant vesicles. Permeability and membrane hydration have been shown to be inversely related to the bending modulus (165). It is suggested that membrane permeability and membrane hydration are related to the ability of the membrane to locally bend so as to create holes for solute permeation. 

The use of the reverse phase evaporation method permits inclusion of 50 and more percent of the substance to be encapsulated from the water phase into the liposomes. Besides, a variety of methods have been developed to obtain lyophilized liposomal preparations possessing good storage stability. The in vitro release rate of different compounds from liposomes, including proteins of moderate molecular weight, is usually under 1% per hour, assuming that the incubation temperature sufficiently differs from the phase transition temperature of a given phospholipid, since the maximal permeability of liposomes is usually observed at temperatures close to the phase transition temperature of the liposomal phospholipid. In vivo, this parameter can vary within wide limits from minutes to hours and depends on the liposome membrane composition, cholesterol content, and disposition within the body. 

F. Barber and J. E. Thompson, Senescence-dependent Increase in the permeability of liposomes prepared from bean cotyledon membranes. 

T. Fluorescein chemiluminescence method for estimation of membrane permeability of liposomes. Anal. Biochem. 2005,342, 338-340. 

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. 

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]. 

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