Partitioning of liposomes

From a formulative point of view, it is important to take into consideration that the base in which liposomes are incorporated could also affect the drug delivery profile as well as the interactions between the liposomes and skin structures. The effect of formulation bases on dyphylline skin permeation from liposomes was examined by Touitou et al. [9]. In this work the effect of four bases for dyphylline liposomes (polyethylene glycol (PEG), carbopol gel, a PEG-enhancer base, and water) was studied. With these bases, the lowest skin permeation flux and a superior skin partitioning of liposomal dyphylline were reported for the PEG base, suggesting that this base favored dyphylline accumulation within the skin. A number of liposomes are currently marketed by cosmetic raw material companies for incorporation in different bases to obtain final products. It is important to keep in mind that the delivery properties of the final formulation could be altered by the vehicle used and should be tested to confirm any performance characteristics claimed. 

C. Quantitative Analysis of Partition of Liposomes in Aqueous Two-Phase Systems... 

The partition of liposomes was investigated using different compositions of gangliosides in the system of 4.0% (w/w) PEO-20/8.0% (w/w) dextran-40 as a function of sodium phosphate concentration. The PEO/dextran two-... 

The mechanism responsible for improved delivery of lipophilic drugs has not yet been clarified. Absorption of liposomes by cells is unlikely. Adsorption to cells followed by slow release of the drug from the liposome, either via diffusion through the thin aqueous tear film or via direct partitioning from the membrane of the vesicle to the membrane of the cell, was proposed as a possible pathway. 

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... 

QSAR studies of the pH-dependent partitioning of acidic and basic drugs into liposomes [64] yielded following equations ... 

Schaper, K.-J., Zhang, H., Raevsky, 0. A. pH-dependent partitioning of acidic and basic drugs into liposomes - a quantitative structure-activity relationship. Quant. Struct.-Act. Relat. 2001, 20, 45-54. 

Avdeef, A., Box, K. J., Comer, J. E., Hibbert, C., Tam, K. Y. pH-metric logP 10. Determination of liposomal membrane-water partition coefficients of ionizable drugs. Pharm. Res. 1998,... 

The octanol-water partition model has several limitations notably, it is not very biological. The alternative use of liposomes (which are vesicles with walls made of a phospholipid bilayer) has become more widespread [149,162,275, 380—4441. Also, liposomes contain the main ingredients found in all biological membranes. 

The determination of partition coefficients using liposomes as a lipid phase require that the sample be equilibrated with a suspension of liposomes, followed by a separation procedure, before the sample is quantitated in the fraction free of the lipid component. 

Figure 5.5 Comparing liposome-water to octanol-water partition coefficients of a series of uncharged substituted benzylalkylamines [387]. The membrane partitioning of the smaller members of the series (n — 0 3) is thought to be dominated by electrostatic and H-bonding effects (enthalpy-driven), whereas the partitioning of the larger members is thought to be directed by hydrophobic forces (entropy-driven) [387]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

Bums, S. T. Khaledi, M. G., Rapid determination of liposome-water partition coefficient (Kiw) using liposome electrokinetic chromatography (LEKC), J. Pharm. Sci. 91, 1601— 1612 (2002). 

Escher, B. I. Schwarzenbach, R. P., Partitioning of substituted phenols in liposome-water, biomembrane-water, and octanol-water systems, Environ. Sci. Tech. 30,260-270(1996). 

Liposome partitioning of ionizable drugs can be determined by titration, and has been correlated with human absorption [102-104]. A new absorption potential parameter has been suggested, as calculated from liposome distribution data and the solubility-dose ratio, which shows an excellent sigmoidal relationship with human passive intestinal absorption (Eq. 2) [102, 103]. 

A further partition system based on the use of liposomes, and marketed as Transil , has also been investigated [105, 106]. 

ESCHER, B. I., SCHWARZENBACH, R. P., Westall, J. C., Evaluation of liposome-water partitioning of organic acids and bases. 2. Comparison of experimental determination methods, Environ. Sci. Technol. 2000, 34, 3962-3968. 

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