Alkaline tea tree oil nanoemulsion nebulizers for the treatment of pneumonia induced by drug-resistant Acinetobacter baumannii

Abstract

The infectious pneumonia induced by drug-resistant Acinetobacter baumannii (DRAB), a hospital-acquired bacterial infection, has a high morbidity and mortality rate. A natural essential oil, tea tree oil (TTO), has a high bactericidal effect without the potential of drug resistance; however, its volatility, hydrophobicity and poor stability limit its applications. Here, TTO nanoemulsions (nanoTTOs) were prepared with the spontaneous-emulsification method. The size of nanoTTOs was 293.2 nm, and the zeta potential was −15.0 mV. They became nebulizers when they were transformed to fine aerosols with a vibrating screen nebulizer. The aerosols had a mass median aerodynamic diameter size of 2.53 μm and a fine particle fraction (1–5 μm) of 86.65%, suitable for pulmonary delivery. The minimum bactericidal concentration (MBC) of nanoTTOs against DRAB was 10.40 mg/mL; while the alkaline nanoTTOs doped with 1.0% NaHCO3 had the MBC of 6.50 mg/mL. Pulmonary delivery of the alkaline nanoTTOs showed obvious therapeutic effects on the DRAB pneumonic mice by downregulating the pro-inflammatory cytokines (IL-1β and IL-6), preventing the bacterial proliferation, and reducing the lung injury, better than ordinary nanoTTOs. Alkaline nanoTTOs are a promising nebulizer formulation for the treatment of bacterial pneumonia, especially drug-resistant bacterial pneumonia.