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

Publication date: Available online 25 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Gabriella Costabile, Romina Provenzano, Alberto Azzalin, Viola Camilla Scoffone, Laurent R. Chiarelli, Valeria Rondelli, Isabelle Grillo, Thomas Zinn, Alexander Lepioshkin, Svetlana Savina, Agnese Miro, Fabiana Quaglia, Vadim Makarov, Tom Coenye, Paola Brocca, Giovanna Riccardi, Silvia Buroni, Francesca UngaroAbstractC109 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 fo...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research