Alterations in the bacterial membrane integrity induced by eu-cl-oflo enhance the bactericidal action of ofloxacin Eudragit E100 potentiates activity of ofloxacin against FQ-resistant Pseudomonas aeruginosa

ROMERO, VL; SANCHEZ, NV; PONS, P; BOCCO, JL; MANZO, RH; ALOVERO, FL

Rosario

Congreso; SAFE XLI Reunión Anual de la Sociedad Argentina de Farmacología experimental; 2009

Sociedad de Farmacologia experimental

The search for new more effective Fluoroquinolones is a constant challenge to overcome the resistance issue. The development of new delivery systems is an alternative tool to preserve the utility of old antimicrobials. Eudragit E100 (Eu) is a cationic polyelectrolyte able to react with the acidic group of drugs. Complexes Eu with Ofloxacin (OFLO) and other counterion, Cl-, which turns the complexes water soluble were prepared, giving clear dispersions (Eu-Cl50-OFLO20) with positive electrokinetic potential and pHs 6.4-6.5. The killing rate and bactericidal action exhibited by OFLO against P.aeruginosa is enhanced in Eu-Cl50-OFLO20. The bacteria were processed for electron microscopy. Those treated with Eu-Cl50-OFLO20 showed damage of bacterial envelope and the cytoplasm was less electrondense. Flow citometry with nucleic acid-binding fluorescent probes show lost membrane integrity. This additional mechanism of action coupled with the own of the FQ could explain the enhancement of the bactericidal action.