Liposome/water partitioning

Octanol" and "Membrane" pK in Partition Coefficients Measurement 67 Tab. 3.1 Octanol-water and liposome-water partition coefficients. ... 

Liposome-water partition potentiometric determinations, 25°C, 0.15 M KCl [8, 71]. Liposomes were made of large (phosphatidylcholine) unilamellar vesicles. 

Liposome-Water Partitioning and the diff 1-2 Approximation in logDyEM-pH Profiles for Monoprotic Molecules... 

TABLE 5.3 Critically Selected Experimental Liposome-Water Partition Coefficients... 

TABLE 5.4 Liposome-Water Partition Coefficients of Substituted Phenols and Other Compounds... 

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., 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. 

Figure 7. Lipophilicity profile of propranolol in liposomes composed of zwitterionic and charged lipids (phosphatidyl ethanolamine (PE), oleic acid (OA), phosphatidyl inositol (PI)). Conditions of measurements are described in [113]. The dotted line indicates the partitioning profile of propranolol in the egg PC liposome system. The bars show the pH-dependent charge profile of propranolol (hatched bars positively charged propranolol) and the lipids in the membrane (black bars negatively charged lipids). Reprinted from [113] Kramer, S. (2001). Liposome/water partitioning , In Pharmacokinetic Optimization in Drug Research, eds. Testa, B. et al. Reproduced by permission of Verlag Helvetica Chimica Acta, Zurich...

The studies on phospholipid bilayers with defined amounts of charged component are helpful to explain the partition characteristics in biological membranes. Liposome water partition data of propranolol in lipids from kidney epithelial cells (a common model system in pharmaceutical sciences for the uptake into the gastrointestinal tract) have been successfully described with partition models developed for pure bilayers or defined mixtures [159]. Since lipophilic cations and anions can be used as probes for the membrane potential, their interaction with microbial and mitochondrial membranes has been studied... 

Kramer, S. (2001). Liposome/water partitioning theory, techniques, and applications. In Pharmacokinetic Optimization in Drug Research Biological, Physicochemical, and Computational Strategies, eds. Testa, B., van Waterbeemd, H., Folkers, G. and Guy, R., Series, Yerlag Helvetica Chimica Acta, Zurich. 

Estimation is easier and less time-consuming because use is made of empirical relationships between the BCF and physicochemical properties of the compound, such as water solubility (S) [42-48], Km, (solid organic carbon/water partition coefficient) [48], Kmw (membrane water partition coefficient), iipw (liposome water partition coefficient) [49], critical micelle concentration (CMC) [45], steric factors, molecular weight [47,48], and others. The most common regression method is the estimation of BCF from the octanol-water partition coefficient (Kovl) [18,42,44-48,50,51],... 

Fujiwara, H., Da, Y.-Z., Ito, K., Takagi, T., Mishioka, Y. (1991) The energy aspect of oil/water partition and its application to the analysis of quantitative structure-activity relationship. Aliphatic alcohols in the liposome/water partition system. Bull. Chem. Soc. Jpn. 64, 3707-3712. 

Kramer SD. Liposome/water partitioning theory, techniques and applications. In Pharmacokinetic Optimization in Drug Research. 

Log Kow is the most widely used descriptor for baseline QSARs but has many disadvantages in the context of our model. First, because octanol does not perfectly mimic the physicochemical properties of biological membranes, there are two different QSAR equations for nonpolar and polar compounds. This complication can be overcome by using the liposome-water partition coefficient log Kupw as the descriptor instead [32]. We therefore recalculated the Kow-based QSARs from the EU Technical Guidance Documents [31] using relationships between log Kow and logKupw for nonpolar (Eq. 9) and polar compounds (Eq. 10), which had been experimentally determined by Vaes et al. [33,34]. 

H. Fujiwara, Y. Z. Da, K. Ito, T. Takagi, and Y. Nishioka, Bull. Chem. Soc. japan, 64, 3707 (1991), The Energy Aspect of Oil/Water Partition and Its Application to the Analysis of Quantitative Structure-Activity Relationships. Aliphatic Alcohols in the Liposome/Water Partition System. 

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