Polymeric Micelles as a Strategy to Enhance the Phototoxic Efficacy of Phenazine Photosensitizers

Antimicrobial photodynamic therapy (aPDT) is a promising therapeutic strategy for treating bacterial infections resistant to conventional antibiotics. In the search for ideal photosensitizers (PSs), we became interested in phenazine compounds, such as Neutral Red (NR) and its halogenated derivative (NRBr). Although they have shown good results in the inactivation of Staphylococcus aureus in their free form, they have some undesirable properties that could be overcome by using drug delivery systems. In this work, we propose the use of polymeric micelles for the development of nanophotosensitizers from Pluronic P123 and F108. The micellar systems developed had a size close to 30-40 nm and allowed us to obtain seven nanophotosensitizers. All of them increased the chemical stability of NRBr and did not modify the stability of NR, which was already stable in buffer solution (pH = 7.4). Furthermore, the Pluronic micelles markedly decreased the aggregation of PSs and increased their photochemical reactivity. The nanophotosensitizers prepared from Pluronic P123 micelles (5% wt/vol) gave the best results and optimized the properties of NR and NRBr. In agreement with that, the new nanophotosensitizers of P123-5% showed better photodynamic inactivation of NR and NRBr against methicillin resistant S. aureus than the free photosensitizers and the other micellar systems. Both photosensitizers loaded into the P123-5% eradicated this microorganism using 30 min of irradiation. Therefore, it is concluded that these polymeric micelles are an excellent alternative for the vehiculization of PSs and that their combination with NR and NRBr enhances the photodynamic efficiency for their use in aPDT.