Mucus-producing epithelial models for investigating the activity of gene delivery systems in the lung.
Fiche publication
Date publication
décembre 2021
Journal
International journal of pharmaceutics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LEBEAU Luc, Pr PONS Françoise
Tous les auteurs :
Sonntag T, Rapp M, Didier P, Lebeau L, Pons F, Casset A
Lien Pubmed
Résumé
Inhaled transfection particles have to penetrate the mucus layer lining the airways to successfully deliver their therapeutic nucleic acid payload to target cells in the underlying epithelium. However, the in vitro models used for evaluating gene carrier efficiency often disregard this viscous defensive barrier. In this study, the two mucus-secreting cell lines NCI-H292 and Calu-3 were selected to develop a series of epithelial models displaying gradual mucus production. In NCI-H292 models, a gradual increase in the MUC5AC mucin was obtained after cell exposure to inducers. In Calu-3 models, MUC5AC production increased as a function of culture duration (3, 7, 14 days) at the air-liquid interface (ALI). Six DOPC-derived cationic lipids were designed and their pDNA delivery activity was evaluated to validate these cellular models. The strongest impairment of the lipid delivery activity was observed in the Calu-3 14-d ALI model. The MUC5AC production in this model was the greatest and the mucus layer was 20 µm thick. The mucus exhibited a solid viscoelastic behaviour, and represented a major hindrance to lipoplex diffusion. The Calu-3 14-d ALI model will be highly useful for accurate evaluation of gene carriers intended for airway administration and characterization of their interactions with the mucus.
Mots clés
airway mucus, cell models, gene delivery, lipoplexes, multiple particle tracking, rheology
Référence
Int J Pharm. 2021 Dec 24;:121423