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

PEREZ, NOELIA; ALTUBE, MARIA JULIA; ROMERO, EDER LILIA; PEREZ, ANA PAULA

Buenos Aires

Conferencia; 1st Zooming Into Preclinical Nanomedicines In The Era Of COVID-19; 2020

Nanomed-AR

The emergence of multidrug resistant pathogens, together with their ability toform biofilms, is a major global health threat requiring novel therapeuticstrategies.To improve the efficacy of Pseudomonas aeruginosa (Pa)infection treatment, we explore a combination therapy between a currentantibiotic (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% eoT, 0.03% TB and 89% H2O, wasstructurally stable along 3 months of storage and after nebulization (~ 195nm 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 thecombined 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. Inconclusion, NAN-eoT-TB may be a successful approach to combatrespiratory tract Pa infections.