Eudragit E100 potentiates activity of Ofloxacin against Fluoroquinolone-resistant Pseudomonas aeruginosa

ROMERO, VL; MANZO, RH; ALOVERO, FL

Tandil

Congreso; XL Reunión Anual SAFE; 2008

Sociedad argentinade Farmacología Experimental

Fluoroquinolones (FQs) resistance is a clinically significant issue. Efforts to improve the efficacy of existing FQs could be an alternative to restrict the development of FQ-resistant bacteria prolonging their future utility. Eudragit E100 (Eu) is a cationic polyelectrolyte able to react with the acidic group of OFLOXACIN yielding Eu-OFLO complexes where OFLO neutralizes 20-50% of the basic groups of Eu. The addition of a second counterion (Cl) turns the complexes water soluble giving clear dispersions (Eu-Cl50-OFLO) with positive electrokinetic potential (ζ) and pHs 6.4-6.5. The activity against FQ-R P.aeruginosa was enhanced exhibiting MICs two or four-fold lower than free OFLO and improved bactericidal effect. Eu-Cl50 without OFLO exhibits an initial antibacterial effect reversible along the time while Eu-Cl50-OFLOx exhibits enhanced effect leading complete bacterial eradication at concentrations or time assays where free OFLO does not show it. This behaviour could be attributed to the improved drug-bacterial cell interaction, topic in which the high ζ of Eu-Cl50-OFLOx could play a preponderant role.