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.

PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection / Costabile, G.; Provenzano, R.; Azzalin, A.; Scoffone, V. C.; Chiarelli, L. R.; Rondelli, V.; Grillo, I.; Zinn, T.; Lepioshkin, A.; Savina, S.; Miro, A.; Quaglia, F.; Makarov, V.; Coenye, T.; Brocca, P.; Riccardi, G.; Buroni, S.; Ungaro, F.. - In: NANOMEDICINE. - ISSN 1549-9634. - 23:(2020), p. 102113. [10.1016/j.nano.2019.102113]

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

Costabile G.
Primo
;
Provenzano R.;Miro A.;Quaglia F.;Ungaro F.
Ultimo
2020

Abstract

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.
2020
PEGylated mucus-penetrating nanocrystals for lung delivery of a new FtsZ inhibitor against Burkholderia cenocepacia infection / Costabile, G.; Provenzano, R.; Azzalin, A.; Scoffone, V. C.; Chiarelli, L. R.; Rondelli, V.; Grillo, I.; Zinn, T.; Lepioshkin, A.; Savina, S.; Miro, A.; Quaglia, F.; Makarov, V.; Coenye, T.; Brocca, P.; Riccardi, G.; Buroni, S.; Ungaro, F.. - In: NANOMEDICINE. - ISSN 1549-9634. - 23:(2020), p. 102113. [10.1016/j.nano.2019.102113]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/776114
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 30
  • ???jsp.display-item.citation.isi??? 26
social impact