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

Abstract

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.

Mathematical Models as Tools to Predict the Release Kinetic of Fluorescein from Lyotropic Colloidal Liquid Crystals

“…This is used to synthesize other different colloidal nanoparticles made up of organic or hybrid materials. These colloidal nanoparticles have a negative Z-potential, as has been previously reported [41,42,43,44,45,46], and the value of the negative charge depends on the medium in which the colloidal nanoparticles are diluted/dispersed, before the analysis, as well as other components of the pharmaceutical formulations [47,48,49,50,51,52,53,54].…”

A mussel-inspired film for adhesion of wet buccal tissue and efficient buccal drug delivery

“…4d), which confirmed that bare PLGA and PLGA-PVA NPs are more likely to bonds with mucin. Likewise, turbidity measurements and mucin absorption percentage were also performed to investigate the interaction between NPs and mucin [41][42][43] ( Supplementary Fig. 5a and 5b), which altogether pointed to the fact that PLGA-PEG and PLGA-PDA NPs interacted much less with mucin than those of bare PLGA and PLGA-PVA NPs.…”

“…between NPs and the mucin particles 40 . Here, we first examined the ability of different NPs to adsorb mucin by probing the variation in average particle size and zeta-potential of NPs 40,41 . When mixed with mucin suspension, bare PLGA and PLGA-PVA NPs showed a significant larger increase in average size compared with PLGA-PEG and PLGA-PDA NPs (Fig.…”

“…Then, the ability of different NPs to penetrate through the mucus layer were quantified by using a Transwell system and agarose gel 40,41 . As the results indicated, the bare PLGA and PLGA-PVA NPs that interacted easily with the mucin particles also showed minimal mucus penetration, whereas PLGA-PEG and PLGA-PDA NPs exhibited much higher translocations across the mucus layer ( Fig.…”

Nanomedicine Approaches for the Pulmonary Treatment of Cystic Fibrosis

“…In this latter case, patients treated with these drugs experienced severe systemic side effects and to boost their efficacy the drugs concentration and their permanence at the lungs, the major site of disease, should be improved. The pulmonary administration of CFTR modulators based on mucus penetrating NPs could be an effective strategy, potentially increasing higher local drug concentrations and minimizing side effects when compared to the oral route of administration (Porsio et al, 2018).…”