UNITEFA   23945
UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Unidad Ejecutora - UE
artículos
Título:
Evaluation of physicochemical properties and bacterial photoinactivation of phenothiazine photosensitizers
Autor/es:
AIASSA, VIRGINIA; GUALDESI, MARÍA S.; VARA, JIMENA; ORTIZ, CRISTINA S.
Revista:
Photochemical and Photobiological Sciences
Editorial:
ROYAL SOC CHEMISTRY
Referencias:
Año: 2019 vol. 18 p. 1576 - 1586
ISSN:
1474-905X
Resumen:
We report herein the physicochemical properties and antimicrobial activity of the new monobrominated derivative Azure B and its parent compound. These dyes are used as photosensitizers for photodynamic therapy and photodynamic antimicrobial chemotherapy.Relevant pharmaceutical properties (pKa, chemical and photochemical stability, and in vitro antimicrobial activity) were determined. A UV-Visible spectrophotometry method was developed and validated according to the International Conference on Harmonization (ICH) guidelines for use in stability indicating studies and determination of the acid dissociation constant of Azure B and its monobrominated derivative. The results showed that both dyes were chemically stable. In addition, the bromination of the phenothiazine dye decreased its photochemical stability and pKa value without affecting the ionization rate at physiological pH.The analytical parameters for validation of the method were: linearity (r2 > 0.9981), limit of detection (LODs) (0.2 ? 0.9 µM), limit of quantification (LOQs) (0.6 ? 2.7 µM), and intra-day precision (0.76 ?1.40%) expressed as relative standard deviation (R.S.D.). The recoveries ranging from 99.5 to 100.9% were obtained for the two dyes. Thus, this method provides a simple, sensitive, accurate, and precise assay for the determination of all compounds.The effect of photosensitizer concentration and visible irradiation time on lethal photosensitization against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were investigated. Both photosensitizers were active against the evaluated bacteria. However, the new monobrominated derivative was more effective than its predecessor and managed to eradicate these microorganisms by using different doses of dye and light. In other words, a lower concentration of AzBBr and irradiation time were required to cause bacterial death equal to or greater than its precursor. The photodynamic efficacy of the two photosensitizers presented the following order: S. aureus E. coli  P. aeruginosa. These studies indicated that the tested dyes satisfy the conditions of potential photosensitizers in terms of physicochemical and antimicrobial properties.