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- W2070900195 abstract "We evaluated fluorescence anisotropy measurements as an alternative technique to estimate drug-lipid membrane partitioning of fluorescent solutes.The lipid bilayer partitioning of six drugs (logP in octanol/water between 2.6 and 5.4) was investigated by fluorescence anisotropy measurements with egg phosphatidylcholine liposomes at pH 7.4. Anisotropy was measured at about 5 and 50μM drug and varying lipid concentrations between 3 and 700μM. Fluorescence was corrected for light scattering and membrane affinities were estimated by non-linear regression analysis of the relative anisotropy as a function of lipid and solute concentrations. Liposome partitioning was in addition determined by equilibrium dialysis and potentiometric titration for comparison.Correction for light scattering by the liposomes was possible to some extent for two drugs. The estimated partition coefficients of three drugs were concentration-independent. For two drugs, membrane saturation was expected at the higher drug concentration. One drug showed significant differences between the parameters estimated at high and low drug concentrations, indicating measurement artifacts. Linear regression between the estimated logarithmic partition coefficients from anisotropy measurements and equilibrium dialysis revealed a slope of 1.05 and an intercept of 1.16 (n=5, r(2)=0.87).Anisotropy measurement with liposomes is hampered by light scattering and pH-dependent fluorescence properties of ionizable drugs. Taking these limitations into account, the technique may offer an alternative to established methods for the estimation of drug membrane partitioning, in particular when potentiometric titration or equilibrium dialysis are not applicable." @default.
- W2070900195 created "2016-06-24" @default.
- W2070900195 creator A5044528459 @default.
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- W2070900195 date "2012-12-01" @default.
- W2070900195 modified "2023-09-25" @default.
- W2070900195 title "Evaluation of fluorescence anisotropy to assess drug–lipid membrane partitioning" @default.
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- W2070900195 doi "https://doi.org/10.1016/j.jpba.2012.08.009" @default.
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