Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

6533b7dafe1ef96bd126d885

RESEARCH PRODUCT

Mucus and Cell-Penetrating Nanoparticles Embedded in Nano-into-Micro Formulations for Pulmonary Delivery of Ivacaftor in Patients with Cystic Fibrosis

Gennara Cavallaro Nicolò Mauro Gaetano Giammona Emanuela Fabiola Craparo Barbara Porsio

subject

Materials science Cystic Fibrosis Nanoparticle 02 engineering and technology Quinolones 010402 general chemistry Aminophenols 01 natural sciences Cystic fibrosis Ivacaftor chemistry.chemical_compound medicine Humans General Materials Science Microparticle Drug Carriers Lung α β-poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA)ivacaftor (VX-770)mucus-penetrating nanoparticle respiratory system 021001 nanoscience & nanotechnology medicine.disease Mucus 0104 chemical sciences Mucus nano-into-micro strategy medicine.anatomical_structure chemistry cell penetrating peptide Cell-penetrating peptide Biophysics Nanoparticles cystic fibrosis artificial mucus (CF-AM)0210 nano-technology Ethylene glycol medicine.drug

description

Here, mucus-penetrating nanoparticles (NPs) for pulmonary administration of ivacaftor in patients with cystic fibrosis (CF) were produced with the dual aim of enhancing ivacaftor delivery to the airway epithelial cells, by rapid diffusion through the mucus barrier, and at the same time, promoting ivacaftor lung cellular uptake. Pegylated and Tat-decorated fluorescent nanoparticles (FNPs) were produced by nanoprecipitation, starting from two synthetic copolymers, and showed nanometric sizes (∼70 nm), a slightly negative ζ potential, and high cytocompatibility toward human bronchial epithelium cells. After having showed the significant presence of poly(ethylene glycol) chains and Tat protein onto the FNP surface, the FNP mucus-penetrating ability, ivacaftor release profile, and lung cellular uptake were studied in the presence of CF-artificial mucus as a function of the FNP surface chemical composition. Moreover, microparticle-based pulmonary drug-delivery systems composed of mucus-penetrating FNPs loaded with ivacaftor and mannitol were prepared by using the nano-into-micro strategy and realized by spray-drying, thereby providing optimal preservation and stabilization of FNP technological and fluorescence properties.

year	journal	country	edition	language
2017-12-26

10.1021/acsami.7b14992 http://hdl.handle.net/10447/256609