Novel strategy anti-Pseudomonas aeruginosa infections: tobramycin- and Thymus vulgaris essential oil delivered by nanostructured archaeolipid nanoparticles

PEREZ NOELIA; ALTUBE MARÍA JULIA; ROMERO EDER LILIA; PEREZ ANA PAULA

Conferencia; 1st Zooming into preclinical nanomedicines in the era Covid19; 2020

The emergence of multidrug resistant pathogens, together with their ability to form biofilms, is a major global health threat requiring novel therapeutic strategies.To improve the efficacy ofPseudomonas aeruginosa (Pa) infection treatment, we explore a combination therapy between a current antibiotic (tobramycin-TB) and Thymus vulgaris essential oil (eoT) delivered bynanostructured archaeolipid nanoparticles (NAN), named as ?NANeoT-TB?. This formulation made of 2% compritol, 0.5% miglyol, 1% archaeolipids extracted from the hyperhalophilic archaebacteria Halorubrum tebenquichense, 3% Tween 80, 5% oT, 0.03% TB and 89% H2O, was structurally stable along 3 months of storage and after nebulization (~ 195 nm Z average, 0.28 pdi, ~ -39 mV).Results from Cryo-TEM, RAMAN spectroscopy and DSC measurements demonstrated that nanoparticles were oval-shaped and that eoT was incorporated in the lipid core as it increased the defects of the lipid crystal lattice. Remarkably, the presence of archaeolipids was critical to improve the TB entrapment and to stabilize the combined trapping of the two active ingredients. On the other hand, NANeoT-TB improved 4 times antibiofilm activity against pre-formed Pa biofilms,in comparison with the same concentration of free eoT and TB. In conclusion, NAN-eoT-TB may be a successful approach to combat respiratory tract Pa infections.