两性喹诺酮抗菌药生理环境下独特的分子荷电性质

本文采用脂质体/水分配系统来考察pH、磷脂的种类和荷电性对药物与有序磷脂膜结合的影响.

Unusual Molecular Charge Property of Amphoteric Quinolones in Physiological Environment

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.