title: Biodegradable nanoparticles meet the bronchial airway barrier: how surface properties affect their interaction with mucus and epithelial cells.
abstract: Despite the wide interest raised by lung administration of nanoparticles (NPs) for the treatment of various diseases, little information is available on their effect toward the airway epithelial barrier function. In this study, the potential damage of the pulmonary epithelium upon exposure to poly(lactide-co-glycolide) (PLGA) NPs has been assessed in vitro using a Calu-3-based model of the bronchial epithelial barrier. Positively and negatively charged as well as neutral PLGA NPs were obtained by coating their surface with chitosan (CS), poloxamer (PF68), or poly(vinyl alcohol) (PVA). The role of NP surface chemistry and charge on the epithelial resistance and mucus turnover, using MUC5AC as a marker, was investigated. The interaction with mucin reduced the penetration of CS- and PVA-coated NPs, while the hydrophilic PF68-coated NPs diffused across the mucus barrier leading to a higher intracellular accumulation. Only CS-coated NPs caused a transient but reversible decrease of the trans-epithelial electrical resistance (TEER). None of the NP formulations increased MUC5AC mRNA expression or the protein levels. These in vitro results highlight the safety of PLGA NPs toward the integrity and function of the bronchial airway barrier and demonstrate the crucial role of NP surface properties to achieve a controlled and sustained delivery of drugs via the pulmonary route.
authors: UMR CNRS 8612, Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Université Paris-Sud, 5 rue Jean-Baptiste Clément, F-92296 Châtenay Malabry cedex, France.
authors: Simona
authors: S
authors: Mura
authors: Hervé
authors: H
authors: Hillaireau
authors: Julien
authors: J
authors: Nicolas
authors: Saadia
authors: S
authors: Kerdine-Römer
authors: Benjamin
authors: B
authors: Le Droumaguet
authors: Claudine
authors: C
authors: Deloménie
authors: Valérie
authors: V
authors: Nicolas
authors: Marc
authors: M
authors: Pallardy
authors: Nicolas
authors: N
authors: Tsapis
authors: Elias
authors: E
authors: Fattal
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D017097:Electric Impedance; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology*; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles; D010539:Permeability; D011100:Polyglycolic Acid / Q000378:metabolism / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid