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Pseudomonas aeruginosa is one of the most refractory organisms to antibiotic treatment and appears to be one of the least susceptible to photodynamic treatment. TMPyP is effective in the photoinactivation of P. aeruginosa, and the co‐administration with the cationic polymer Eudragit®‐E100 (Eu) potentiates this effect against isolates both sensitive and resistant to antibiotics. The fluorescent population (>98%) observed by flow cytometry after exposure to Eu + TMPyP remained unchanged after successive washings, indicating a stronger interaction/internalization of TMPyP in the bacteria, which could be attributed to the rapid neutralization of surface charges. TMPyP and Eu produced depolarization of the cytoplasmic membrane, which increased when both cationic compounds were combined. Using confocal laser scanning microscopy, heterogeneously distributed fluorescent areas were observed after TMPyP exposure, while homogeneous fluorescence and enhanced intensity were observed with Eu + TMPyP. The polymer caused alterations in the bacterial envelopes that contributed to a deeper and more homogeneous interaction/internalization of TMPyP, leading to a higher probability of damage by cytotoxic ROS and explaining the enhanced result of photodynamic inactivation. Therefore, Eu acts as an adjuvant without being by itself capable of eradicating this pathogen. Moreover, compared with other therapies, this combinatorial strategy with a polymer approved for pharmaceutical applications presents advantages in terms of toxicity risks. [ABSTRACT FROM AUTHOR]

We report the enhanced bactericidal activity of ofloxacin in drug-containing Eudragit E100® dispersions ( Eu Cl- OFX) against Pseudomonas aeruginosa and the effect of the cationic polymer on bacterial membrane. Organisms treated with Eu Cl- 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 Eu Cl- 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 Eu Cl- 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. [ABSTRACT FROM AUTHOR]