PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection.

Autor: Costabile G; Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Provenzano R; Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Azzalin A; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Pavia, Italy., Scoffone VC; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Pavia, Italy., Chiarelli LR; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Pavia, Italy., Rondelli V; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Segrate, (MI), Italy., Grillo I; Institut Laue-Langevin, Grenoble, France., Zinn T; ESRF-The European Synchrotron, Grenoble, France., Lepioshkin A; Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Savina S; Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Miro A; Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Quaglia F; Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy., Makarov V; Federal Research Centre 'Fundamentals of Biotechnology' of the Russian Academy of Sciences, Moscow, Russia., Coenye T; Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium., Brocca P; Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan, Segrate, (MI), Italy., Riccardi G; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Pavia, Italy., Buroni S; Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia, Pavia, Italy. Electronic address: silvia.buroni@unipv.it., Ungaro F; Department of Pharmacy, University of Napoli 'Federico II', Napoli, Italy. Electronic address: ungaro@unina.it.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2020 Jan; Vol. 23, pp. 102113. Date of Electronic Publication: 2019 Oct 25.
DOI: 10.1016/j.nano.2019.102113
Abstrakt: C109 is a potent but poorly soluble FtsZ inhibitor displaying promising activity against Burkholderia cenocepacia, a high-risk pathogen for cystic fibrosis (CF) sufferers. To harness C109 for inhalation, we developed nanocrystal-embedded dry powders for inhalation suspension consisting in C109 nanocrystals stabilized with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) embedded in hydroxypropyl-β-cyclodextrin (CD). The powders could be safely re-dispersed in water for in vitro aerosolization. Owing to the presence of a PEG shell, the rod shape and the peculiar aspect ratio, C109 nanocrystals were able to diffuse through artificial CF mucus. The promising technological features were completed by encouraging in vitro/in vivo effects. The formulations displayed no toxicity towards human bronchial epithelial cells and were active against planktonic and sessile B. cenocepacia strains. The efficacy of C109 nanosuspensions in combination with piperacillin was confirmed in a Galleria mellonella infection model, strengthening their potential for combined therapy of B. cenocepacia lung infections.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: