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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., (© 2023 American Society for Photobiology.)

The development and characterization of a novel, gel-type material based on a dendronized polymer (DP) loaded with ciprofloxacin (CIP), and the evaluation of its possible use for controlled drug release, are presented in this work. DP showed biocompatible and non-toxic behaviors in cultured cells, both of which are considered optimal properties for the design of a final material for biomedical applications. These results were encouraging for the use of the polymer loaded with CIP (as a drug model), under gel form, in the development of a new controlled-release system to be evaluated for topical administration. First, DP-CIP ionic complexes were obtained by an acid-base reaction using the high density of carboxylic acid groups of the DP and the amine groups of the CIP. The complexes obtained in the solid state were broadly characterized using FTIR spectroscopy, XRP diffraction, DSC-TG analysis and optical microscopy techniques. Gels based on the DP-CIP complexes were easily prepared and presented excellent mechanical behaviors. In addition, optimal properties for application on mucosal membranes and skin were achieved due to their high biocompatibility and acute skin non-irritation. Slow and sustained release of CIP toward simulated physiological fluids was observed in the assays (in vitro), attributed to ion exchange phenomenon and to the drug reservoir effect. An in vitro bacterial growth inhibition assay showed significant CIP activity, corresponding to 38 and 58% of that exhibited by a CIP hydrochloride solution at similar CIP concentrations, against Staphylococcus aureus and Pseudomonas aeruginosa, respectively. However, CIP delivery was appropriate, both in terms of magnitude and velocity to allow for a bactericidal effect. In conclusion, the final product showed promising behavior, which could be exploited for the treatment of topical and mucosal opportunistic infections in human or veterinary applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)