Immobilized drug partitioning

C Lagerquist, F Beigi, A Karlen, H Lennernas, P Lundahl. Effects of cholesterol and model transmembrane proteins on drug partitioning into lipid bilayers as analyzed by immobilized-liposome chromatography. J Pharm Pharmacol 53 1477-1487, 2001. 

F Beigi, Q Yang, P Lundahl. Immobilized-liposome chromatographic analysis of drug partitioning into lipid bilayers. J Chromatogr A 704 315-321, 1995. 

Danelian E, Karlen A, Karlsson R et al. (2000) SPR biosensor studies of the direct interaction between 27 drugs and a liposome surface correlation with fraction absorbed in humans. J Med Chem 43 2083-2086 Engvall C, Lundahl P (2004) Drug partitioning on immobilized porcine intestinal brush border membranes. J Chrom A 1031 107-112... 

A very promising method, immobilized artificial membrane (IAM) chromatography, was developed by Pidgeon and co-workers [299-304,307], where silica resin was modified by covalent attachment of phospholipid-like groups to the surface. The retention parameters mimic the partitioning of drugs into phospholipid bilayers. The topic has been widely reviewed [47,298,307,309-311]. 

Ong, S. Liu, H. Pidgeon, C., Immobilized-artificial-membrane chromatography Measurements of membrane partition coefficient and predicting drug membrane permeability, J. Chromatogr. A 728, 113-128 (1996). 

Barbato, F. La Rotonda, M. I. Quaglia, E, Interactions of nonsteroidal antiinflammatory drugs with phospholipids comparison between octanol/buffer partition coefficients and chromatographic indexes on immobilized artificial membranes, J. Pharm. Sci. 86, 225-229 (1997). 

Immobilized artificial membranes (IAM) are another means of measuring lipophilic characteristics of drug candidates and other chemicals [90-94], IAM columns may better mimic membrane interactions than the isotropic octanol/water or other solvent/solvent partitioning system. These chromatographic indices appear to be a significant predictor of passive absorption through the rat intestine [95]. 

The basic principle is shared by several methods In chromatographic or electrophoretic systems where the liposomes (vesicles) are immobilized, pseudostationary, or carried by an electroendosmotic flow, migrating amphiphilic drug molecules partition between the water outside the liposomes, the lipid bilayer of the liposome, and the aqueous compartment within the liposome (Fig. 3). In all cases the migration rate basically reflects the par-... 

X-Y Liu, Q Yang, N Kamo, J Miyake. Effect of liposome type and membrane fluidity on drug-membrane partitioning analyzed by immobilized liposome chromatography. J Chromatogr A 913 123-131, 2001. 

Q Yang, X-Y Liu, S-i Ajiki, M Hara, P Lundahl, J Miyake. Avidin-biotin immobilization of unilamellar liposomes in gel beads for chromatographic analysis of drug-membrane partitioning. J Chromatogr B 707 131-141, 1998. 

The partition coefficients of triphenylalkylphosphonium homologs have been determined in gel bead-immobilized small or large unilamellar liposomes by chromatography [8]. It was claimed that the technique, immobilized liposome chromatography (ILC), is suitable for the determination of membrane partition coefficients of drugs. 

Support for these results comes from a paper in which the partitioning of 17 dmgs into adipose tissue was examined [84]. For these drugs, log Poct, log Doct atpH 74, and the retention time on an immobilized artificial membrane, log k IAM, were determined. The adipose storage index (ASI) was defined as ... 

A drug is absorbed through diffusion across a series of separate barriers where the single layer of epithelial cells is the most significant barrier to absorption. Many in vitro methods have been developed for the study of this phenomenon. These methods include small animal gut studies, cell culture (i.e., Caco-2 cell culture model), octanol-water partition coefficients, measures of hydrogen bonding and desolvation energies, immobilized artificial membranes, and retention time on reversed-phase HPLC columns. 

The microsealed delivery device is a variation of the matrix-type transdermal system in which the drug is dispersed in a reservoir phase which is then immobilized as discrete droplets in a cross-linked polymeric matrix. Release can be further controlled by inclusion of a polymeric microporous membrane. This system therefore combines the principles of both the liquid reservoir and matrix-type devices. Rate of release of a drug from a microsealed delivery system is dependent on the partition coefficient between the reservoir droplets and the polymeric matrix the diffusivity of the drug in the reservoir, the matrix and the controlling membrane and on the solubility of the drug in the various phases. There are, obviously, many ways to achieve the desired zero-order release rate, but only nitroglycerin has been commercially formulated into this type of delivery device (Karim 1983). 

Immobilized artificial membrane (lAM) stationary phase consists of a monolayer of phospholipid covalently immobilized on an inert silica support. The lAM stationary phase mimics the lipid environment found in cell membranes, and it can be used for elucidating drug-membrane interactions. The interaction of catechins, flavones, flavonols, anthocyanidins, and anthocyanins with phosphatidylcholine was investigated by HPLC with an lAM colunm. The lAM partition coefficients of the flavonoids correlated well with the amounts flavonoids incorporation into the liposomes [42]. 

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