Strategies to improve PDT inactivation response in biofilms

Emerging and re-emerging infectious diseases are growing in a faster rate. Antimicrobial resistance is one relevant factor contributing to the re-merging infections. New pathogens or the lack of control of infectious diseases result in great consequences for the healthcare. In the majority of the infectious (70-75%), the microorganisms are present in the biofilm form. Biofilm is a well-organized community of microorganisms where the cells are involved by a structured and protective extracellular matrix (ECM), resulting in less tolerance to antimicrobial treatments. Antimicrobial photodynamic therapy (aPDT) has been presented as an attractive alternative to the antibiotics for the treatment of several infectious diseases, caused by a diversity of bacteria, fungus, and virus. Likewise, the response behavior to the antibiotics, the photodynamic inactivation (PDI) shows lower response in the biofilm, when compared to the one observed with the same microorganism in suspension. Due to this fact, aPDT may not show efficacy in the treatment of some infected tissues, so the development of different strategies to improve PDI in biofilms are needed to allow a higher potential of clinical success. In this presentation we will discuss different PDI protocols using distinct strategies to overcome the protective action of the ECM to achieve a higher and homogenous photosensitizer distribution within the whole biofilm thickness, as well as to achieve higher inactivation response in Staphylococcus aureus, Pseudomonas aeruginosa, and Rhyzopus oryzae biofilms. The investigated strategies were: sonophotodynamic therapy, and association with inorganic salt (KI), surfactant, nanodelivery platforms or enzyme. Inactivation results show that the efficacy of the different strategies is related to specific microorganism biofilm. In this sense, due to the high diversity of microorganism cells, as well as its ECM and biofilm characteristics, aPDT protocol must be individualized considering specificities of the target infectious disease.