Nanoaerosols reduce required effective dose of liposomal levofloxacin against pulmonary murine Francisella tularensis subsp. novicida infection.

Monique L Van Hoek,Igor L Kanev,Crystal N Propst,Albert O Nwabueze,Victor N Morozov,Bradford W Gutting,Rachel E Pepin

doi:10.1186/s12951-016-0182-0

Abstract

BackgroundThe Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator. This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. novicida (F. novicida) infections in BALB/c mice.ResultsFirst, the analysis of quantum dots distribution in cryosections of murine lungs demonstrated that nanoaerosols penetrate the alveoli and spread more homogenously in the lungs than upon intranasal delivery. Second, the generator was used to aerosolize the antibiotic levofloxacin to determine the effectiveness of nanoaerosolized levofloxacin as treatment against F. novicida. The generator was capable of delivering a sufficient dose of nanoaerosolized liposome-encapsulated levofloxacin to rescue mice against 100LD50 of F. novicida.ConclusionsThe nanoaerosol-delivered dosage of liposome-encapsulated levofloxacin required to rescue mice is approximately 94× lower than the oral required dose and approximately 8× lower than the intraperitoneal dose required for rescue. In addition, treatment with nanoaerosols consumes less total volume of therapeutic solutions and is gentler on sprayed material than the aerosolization by a conventional three-jet Collison nebulizer as seen by the preservation of liposomes. This could represent a significant advance for the use of expensive therapeutics and lung directed therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0182-0) contains supplementary material, which is available to authorized users.

Highlights

The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator
This study investigated the utility of a nanoaerosolbased therapeutic approach using levofloxacin against a murine pulmonary Francisella infection as a model
Previous studies show that Francisella targets alveolar type II epithelial cells and macrophages during pulmonary infections so the ability to deliver therapeutics directly to the alveoli would be beneficial [24,25,26]

Summary

Introduction

The Institute of Theoretical and Experimental Biophysics in Moscow recently developed a new nanoaerosol generator This study evaluated this novel technology, which has the potential to enhance therapeutic delivery, with the goal of using the generator to treat pulmonary Francisella tularensis subsp. The Institute of Theoretical and Experimental Biophysics (ITEB) in Moscow has developed a new technology for the generation of nanoaerosolized biological materials, which can retain structural and functional properties of the molecules [5, 6]. This technology is based on the electrohydrodynamic atomization of a solution followed by gas-phase neutralization of the electrospray–generated ions and nanoclusters with oppositely charged ions generated via the same technique. The full list of parameters and their effects are discussed in the references presented above

Methods

Results

Conclusion