Eudragit E100® potentiates the bactericidal action of ofloxacin against fluoroquinolone-resistant Pseudomonas aeruginosa

Abstract

We report the enhanced bactericidal activity of ofloxacin in drug‐containing Eudragit E100® dispersions (EuCl‐OFX) against Pseudomonas aeruginosa and the effect of the cationic polymer on bacterial membrane. Organisms treated with EuCl‐OFX showed changes in cell morphology, altered outer membrane (OM) and cytoplasm with low electrodensity areas. Zeta potential of bacterial surface was shifted to positive. Sensitization to lytic agents was also observed. A profound effect on bacterial size, granularity and membrane depolarization was found by flow cytometry. Cultures exposed to drug‐free polymer also showed some damaged bacterial membranes, but there was no significant cell death. Inhibition of P. aeruginosa by EuCl‐OFX may involve surface effect and, to some extent, permeation effect. The cationic polymer act to mitigate the electronegativity of cell surface in the process of disorganizing the OM, rendering it more permeable to antibiotic. In addition, cytoplasmic membrane depolarization turns bacterial cell more vulnerable. The effects on membranes combined with the mechanism of action of quinolone explain the improved bactericidal action exhibited by EuCl‐OFX. The behavior described for Eudragit E100® against P. aeruginosa may be a useful tool to broaden the spectrum of antibiotics whose clinical use is limited by the impermeability of the bacterial OM.

PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human pathogens

“…3C and 4). Accordingly, enhanced bacterial uptake of OFX loaded bioadhesive hydrogels or OFX-containing Eudragit E100 ® dispersions were reported to increase bactericidal properties against P. aeruginosa [29,30]. In the present study, OFX-mPEG-PLGA nanoparticles consistently showed better bactericidal activity against all the tested pathogenic bacterial strains, as revealed by the severe reduction in the number of colonies than the free drug or OFX-PLGA nanoparticles ( Fig.…”

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations

“…EuE100 spectrum presents the characteristic bands at 1730 and 2770-2820 cm À1 associated to ester and diethylamine groups. 40 On the other hand, EuS100 peaks are observed: 2950, 1730 and 1450 cm À1 due to carboxylic oxydryl, ester and methyl groups, respectively. 41 Black arrows indicate shifts from 1780-1730 to 1760 cm À1 which can be associated to polymers interactions related to the blend formation.…”

Evaluation of the Antimicrobial Activity of Cationic Peptides Loaded in Surface-Modified Nanoliposomes against Foodborne Bacteria

“…Previous studies have shown that Eudragit shows a membrane-destabilising effect that is expressed as a perturbation of the membrane structure allowing the passage of water-soluble molecules, and also antiviral effects against the herpes simplex virus type 2 (HSV-2) [37]. Formulations with traditional antibiotics have also been described using Eudragit to increase their activity against P. aeruginosa with fluoroquinolone resistance [38]. Therefore, the encapsulation of the peptide +2 and the peptide +5 into CL increases the activity by 2083 (peptide+2/CL-peptide+2) and 1562 times (peptide+5/CL-peptide+5) against L. monocytogenes .…”