Nebulizable nanostructured archaeolipid carriers delivering tobramycin and Thymus vulgaris essential oil: Anti-biofilm, anti-oxidant and anti-inflammatory activity

NOELIA PEREZ; EDER ROMERO; ANA PAULA PEREZ

Congreso; Reunión de sociedades de biociencias 2021; 2021

SAIC, SAI, AAFE, NANOMED-AR

Lung infections with Pseudomonas aeruginosa (Pa) in cystic fibrosis patients are persistent due to their ability to grow in biofilms, that protect bacteria from host defenses and chemotherapy. Pa infections, together with chronic airway inflammation, diminish the quality of life of patients who often require aggressive treatments that frequently fail to eradicate the infection. Thus, development of novel therapeutic strategies is urgent. We developed NAC eoT-TB, a formulation that combines the broad spectrum antibiotic tobramycin (TB) and Thymus vulgaris essential oil (eoT) -which has anti-inflammatory and antioxidant properties- delivered by nanostructured archaeolipid carriers (NAC). NAC eoT-TB (195 ± 15 nm, -39 ± 4 mV), were structurally stable after nebulization, an important feature for an efficient delivery to the lungs by inhalation route. The use of essential oil as pharmaceutical ingredient can be limited by its high volatility. However, the incorporation of eoT into NAC eoT-TB decreased its evaporation rate 1.7 times after 24 h at room temperature. On the other hand, while the viability of bacteria in established Pa biofilm was reduced in a similar degree by NAC eoT-TB and free TB, the former significantly decreased the biomass of the biofilm (86 ± 11% vs 39 ± 59%, respectively, at 18 µg/ml of TB). At these concentrations, NAC eoT-TB did not significantly reduce the viability of human alveolar basal epithelial cells (A549), neither human macrophages (THP1). Also, A549 cells stimulated with 1 µg/ml LPS showed an improved antioxidant activity of 182 µg/ml eoT delivered by NAC eoT-TB which reduced 96 ± 7% of ROS generation, whereas free eoT reduced only 61 ± 51%. In addition, the incubation of THP1 with NAC eoT-TB significantly diminished the release of proinflammatory cytokine TNF-α. In summary, these results indicate NAC eoT-TB has improved antibiofilm, antioxidant and anti-inflammatory activity compared to free eoT and TB, and therefore it may be a successful approach to combat Pa infections.