Estratégias para superação da barreira do surfactante pulmonar para sucesso da terapia fotodinâmica antimicrobiana

Abstract

Pneumonia is an infection characterized by inflammation of the alveoli that is filled with fluid or pus, making breathing and the passage of oxygen into the bloodstream difficult. This infection is among the main causes of morbidity and mortality, mainly due to the difficulty in finding effective treatments given the increase in the rate of antibioticresistant microorganisms. Antimicrobial Photodynamic Therapy (aPDT) presents itself as a potential alternative, due to its high antimicrobial efficiency and non-specific action acting on multiple molecular targets, selectivity to the treatment site and through noninvasive procedure. Studies carried out by our research group reported the efficiency and safety of a protocol for in vitro photoinactivation of Streptococcus pneumoniae, as well as the delivery of light and photosensitizer in an animal model. However, the reduction of microorganisms in vivo still presents challenges to be overcome, due to the presence of lung surfactant (LS), which traps photosensitizer (PS) molecules preventing them from interacting with the microbial target. In the present study, different approaches were used in order to optimize the antimicrobial response of aPDT using indocyanine green (ICG) in the presence of LS, where this FS was associated with perfluorocarbon and oxygen nanobubbles, in addition to the combination of aPDT with ultrasound. However, the most promising strategy consisted of the combination of ICG (10 µM) with the Gantrez AN-139 polymer (0.2% (w/v)), which showed high microbial reduction of S. pneumoniae concomitantly with nontoxicity for lung cell lines human fibroblast (MRC-9) and epithelial (A549), under same treatment conditions. The achieved results demonstrate the difficulties in developing protocols for lung disinfection and point to a possible solution for optimizing the antimicrobial response of aPDT for this purpose.