The thermodynamic partitioning behavior of solutes into immobilized artificial membrane(IAM) and n-octanol/water systems was investigated, including acidic,basic,and amphoteric substances.In an n-octanol/buffer system,partitioning process was entropy-dominated for the most studied drugs,while partitioning of oxolinic and nalidixic acids into n-octanol phase was enthalpy-driven.In IAM chromatography,partitioning into membrane for the studied solutes was enthalpy-driven and an exothermal process.In conclusion,there is a significant difference of solutes′ partitioning mechanism into either IAM or an n-octanol phase,therefore,presenting the theoretical basis for differing lipophilicity measuring scale.
In this paper the effect of the unusual molecular charge property of amphoteric quinolones,including grepafloxacin and olamufloxacin,on the binding to the negatively charged lipid membrane under the physiological conditions was investigated.The subtle pH variation around 7.4 can significantly change the molecular charge property of the two amphoteric quinolones,which results in a significant change of the electrostatic forces.The liposome/water system was undertaken to measure the drug-phospholipid membrane interactions.In the liquid-crystal liposome,the binding to membrane of the two quinolones was increased in the negatively charged liposome while decreased in the neutral liposome,with pH from 7.4 to 6.8.Similarly,the same tendency occurred in the gel-state liposome,that the binding to membrane increased in the negatively charged liposome from 7.4 to 6.8,mimicking drug transfer process from extracellular into intracellular fluid.In conclusion,the molecular electrical charge for amphoteric quinolones was very sensitive to pH variation around physiological pH,which may play an important role in the in vivo drug pharmacokinetics.
