| 1. |
- Beigi, Farideh, et al.
(författare)
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Immobilized liposome and biomembrane partitioning chromatography of drugs for prediction of drug transport
- 1998
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 164:1-2, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- Drug partitioning into lipid bilayers was studied by chromatography on liposomes and biomembranes immobilized in gel beads by freeze–thawing. The drug retention volume was expressed as a capacity factor, Ks, normalized with respect to the amount of immobilized phospholipid. Log Ks values for positively charged drugs on brain phosphatidylserine (PS)/egg phosphatidylcholine (PC) liposomes decreased as the ionic strength was increased, increased as the PS:PC ratio or the pH was increased and varied linearly with the temperature. Log Ks values for beta-blockers, phenothiazines and benzodiazepines on egg phospholipid (EPL) liposomes correlated well with corresponding values on red cell membrane lipid liposomes (r2=0.96), and on human red cell membrane vesicles containing transmembrane proteins (r2=0.96). A fair correlation was observed between the values on EPL liposomes and those on native membranes of adsorbed red cells (r2=0.86). Compared to the data obtained with liposomes, the retentions of hydrophilic drugs became larger and the range of log Ks values more narrow on the vesicles and the membranes, which expose hydrophilic protein surfaces and oligosaccharides. Lower correlations were observed between drug retention on EPL liposomes and egg PC liposomes; and between retention on liposomes (or vesicles) and immobilized artificial membrane (IAM) monolayers of PC analogues. Absorption of orally administered drugs in humans (literature data) was nearly complete for drugs of log Ks values in the interval 1.2–2.5 on vesicles. Both vesicles and liposomes can thus be used for chromatographic analysis of drug–membrane interaction and prediction of drug absorption.
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| 2. |
- Zhang, Yanxiao
(författare)
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Chromatographic studies of interactions between solutes, lipid bilayers and the glucose transporter Glut1
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is advantageous to analyze solute interactions with biological membranes by chromatography on stationary phases that mimic the membrane structures. In the present work, liposomes, proteoliposomes, human red cells and red cell membrane vesicles were immobilized for analyses ofinteractions between solutes (peptides, drugs, inhibitors and glucose), lipid bilayers and theglucose transporter Glut1.For microscale analysis of solute-membrane interactions, liposomes were immobilized incontinuous beds for capillary chromatography and included in the running buffer as pseudostationary phase in capillary electrophoresis. These techniques were convenient and rapid. Inchromatographic drug partitioning studies, the logarithm of the specific capacity factors determined on liposomes in capillary continuous beds showed a linear correlation with the logarithmof apparent drug permeabilities through Caco-2 epithelial cell monolayers.Peptide and drug interactions with lipid bilayers were analyzed by chromatography on liposomes immobilized in gel beads. The retardations of peptides corresponding to segments ofGlut1 were related to the transfer free energy distribution within the peptides and to the hydrophobicities of the peptides. The effects of pH. temperature, ionic strength, flow rate and phospholipid composition on the retardation of drugs on liposomes or membrane vesicles were studied.For the first time, human red cells were immobilized in gel particles for chromatographicactivity analyses. D-Glucose showed a larger retardation than L-glucose upon transport retentionchromatography and Glut1 in the cells showed high affinities for D-glucose and forskolin, asdetermined by frontal affinity analyses.For exceptionally stable immobilization, biotin-avidin binding was introduced. Glut1 inproteoliposomes immobilized by this method showed solute affinities similar to those of sterically immobilized proteoliposomes.
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