Interaction of Grepafloxacin with Large Unilamellar Liposomes:  Partition and Fluorescence Studies Reveal the Importance of Charge Interactions

• Published in: Langmuir Vol. 18; no. 26; pp. 10231 - 10236
• Main Authors: Rodrigues, Catarina, Gameiro, Paula, Reis, Salette, Lima, J. L. F. C, de Castro, Baltazar
• Format: Journal Article
• Language: English
• Published: American Chemical Society 24-12-2002
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la0205093

The partition and location of grepafloxacin, a “second-generation” fluoroquinolone with enhanced efficacy against Gram(+) bacteria, in bilayers of dimyristoyl-l-α-phosphatidylcholine and dimyristoyl-l-α-phosphatidylglycerol have been studied by spectrophotometric and fluorimetric methods, and the partition coefficients (K p) have also been determined by conventional drug quantification after phase separation. The K p values obtained by the different methods are identical within experimental error and were found to be larger than those reported for other fluoroquinolones, which is attributed to the less acidic character of grepafloxacin caused by the methyl substituents in the heterocyclic and the piperazine rings. Thus, at the physiological pH grepafloxacin exists 20% in the cationic form, in contrast to what happens to other fluoroquinolones for which only the zwitterionic and anionic forms exist to any appreciable extent at pH 7.4. The fluorescence studies have also revealed that grepafloxacin is not deeply buried inside the lipid bilayers, despite the presence of the two methyl groups, but is located near the phospholipid headgroups, as has been found with other fluoroquinolones. Furthermore, our data suggest that the enhanced Gram(+) activity of grepafloxacin can be due to the charge interaction that occurs between the cationic form of the drug and the negatively charged membrane surface of the Gram(+) bacteria at physiological pH.