Overcoming the Pulmonary Surfactant Barrier with ICG-Chitosan for Antimicrobial Photodynamic Therapy

Antimicrobial Photodynamic Therapy (aPDT) has been investigated as an alternative approach for treating pulmonary infections. However, components of the pulmonary environment, particularly pulmonary surfactant, may interfere with photosensitizer availability and compromise the photodynamic response. Therefore, carrier systems capable of preserving indocyanine green (ICG) activity under these conditions are of interest. In this study, chitosan (CS) was evaluated as a carrier for ICG to improve its performance in the presence of pulmonary surfactant. The ICG-CS formulation was characterized by absorption and fluorescence spectroscopy, and its behavior during irradiation was assessed through photodegradation experiments. Absorption measurements were performed in the ultraviolet-visible and near-infrared regions, whereas fluorescence was evaluated after excitation at 780 nm. Photodegradation was monitored under increasing light doses to compare free ICG with CS-associated ICG. Photodynamic activity was evaluated against Streptococcus pneumoniae using 10 µM ICG associated with different CS concentrations and irradiation at 808 nm. Association with CS modified the photophysical profile of ICG while maintaining absorption within the spectral region suitable for excitation at 808 nm and reducing fluorescence intensity. During irradiation, ICG-CS showed a gradual decrease in absorbance than free ICG. In microbiological assays performed in the presence of pulmonary surfactant, CS concentration influenced the photodynamic response. The formulation containing 10 µM ICG and 0.3% CS showed the best performance, producing a 6.83 log10 CFU/mL reduction after 10 J/cm² and reaching the detection limit of the method. In comparison, 0.2% CS showed lower activity at the same dose, with increased bacterial inactivation from 15 J/cm². These results indicate that CS association modifies ICG photophysical behavior and favors its photodynamic activity in the presence of pulmonary surfactant. S. pneumoniae inactivation achieved at a low light dose supports the potential of ICG-CS for aPDT approaches targeting pulmonary infections under conditions that mimic barriers within the pulmonary microenvironment