Liposome partition coefficient

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

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,... 

A method where phospholipids are entrapped in the pores of resin beads, in the forms of multilamellar vesicles, has been described [313-319,376]. In some ways, the idea is similar to that of IAM chromatography, even though the resin is modified differently. The retention indices correlate very well with the partition coefficients measured in liposome-water systems (described below). 

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 5.3 The effect of hydrogen bonding and steric hindrance on the difference between liposome-water and octanol-water partition coefficients 8 increased H-bond donor strength and decreased steric hindrance favor membrane partitioning in the substituted phenols [381]. [Avdeef, A., Cun Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

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

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

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. 

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). 

Principal differences between bulk media water and membrane water partition coefficients are listed in Table 2. These differences are essentially based on the several orders of magnitude difference in surface-to-volume ratio. In the liposomal system, charges built up due to sorption of charged species can be electrically neutralised by counter-ions from the electrolyte (diffuse double... 

Yang, Q., Liu, X. Y., Umetani, K., Kamo, N. and Miyake, J. (1999). Partitioning of triphenylalkylphosphonium homologues in gel bead-immobilized liposomes chromatographic measurement of their membrane partition coefficients, Biochim. Biophys. Acta-Biomem., 1417, 122-130. 

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],... 

The role of the ammonium salt anion is not the loading of the amphipathic weak base per se, but rather to control the stability of loading and the profile and rate of release of the amphipathic weak base from the liposome to the external aqueous phase. Two major factors that differentiate the different anions are, firstly, their ability to induce precipitation/crystallization/ gelation in the intraliposome aqueous phase (1,12), and secondly, their effect on the membrane/buffer and octanol/buffer partition coefficient of the amphipathic weak base (1). Regarding the precipitation, the higher the amount of precipitated amphipathic weak base, the more stable is the loading and the slower is its release rate (10-12,18,33,35) and (Wasserman et al.). There are also some risks involved in the precipitation which in some cases reduce the mechanical stability of the liposomes and change liposome shape (36). 

The octanol/buffer represents a partition coefficient between two bulk phases it is less affected by the structure of the analyte and therefore it cannot be used to predict the exact value of liposome membrane-to-buffer Xp, which is also affected by the geometry of the analyte (41 4). However, it is accepted and established that the octanol-to-buffer can help to predict transmembrane passive diffusion (40). In the case of liposomes such as Doxil, in which the internal aqueous phase (intraliposome aqueous phase) is different from the external liposome aqueous medium due to large differences in the composition and pH of these two aqueous phases, there are two different liposome membrane-to-aqueous phase partition coefficients this is referred to as asymmetry in the membrane-to-aqueous media partition coefficient. 

Takagi, T., Kimura, A., Da, Y. Z., Nakai, H., and Fujiwara, H. Partition coefficients in a liposome/water system. Methods for determination and error analysis, Anal Scl, 8(6) 761-765, 1992. 

A Avdeef, KJ Box, JEA Comer, C Hibbert, KY Tam. pH-Metric log P 10. Determination of liposomal membrane-water partition coefficients of ioniz-able drugs. Pharm Res 15 209-215, 1998. 

Liao, K. and Yin, M., Individual and combined antioxidant effects of seven phenolic agents in human erythrocyte membrane ghosts and phosphatidylcholine liposome systems importance of the partition coefficient, J. Agric. Food Chem., 48, 2266, 2000. 

Table 10.2 Organic Phase-Water Partition Coefficients of Some Organic Compounds for Various Organic Phases Octanol (o), Triacylglycerides (tag), Liposomes (lips), Proteins (prot), Cutin (cut), and Lignin (lig). (All values except Kiow in L kg"1 org. phase for 20-25°C if not otherwise stated. Note that the densities of the organic phases are close to 1 kg org. phase L 1 org. phase.)...

Figure 10.13 Plot of log 1/LC,S0 for guppies (small tropical fish, Poecilia reticulata) versus (a) log octanol-water partition constant (log A ,ow), and (b) log L-a-dimyristoylphosphatidylcholine liposome-water coefficient (log A)]ipsw) for a series of neutral apolar and weakly polar (o) and polar (t) compounds. Data from Gobas et al. (1988), Vaes et al. (1998), and Gunatilleka and Poole (1999).

---