title: About the impact of water movement on the permeation behaviour of nanoparticles in mucus.
abstract: The purpose of this study was to establish a method to evaluate the diffusion behaviour of nanoparticles (NP) in mucus taking also the water movement into account. For this purpose, NP based on different chitosan derivatives, either thiolated or not, and marked with fluorescein diacetate were prepared by ionotropic gelation with hyaluronan. NP size and polydispersity were in the respective intervals 363.5±33.3-385.7±36.5nm, and 0.35±0.11-0.39±0.10. An in vitro study of water-assisted NP transport through mucus was realized by filling the barrel of a syringe kept in vertical position, tip down, with mucus. Then a bottom-to-surface PBS flow across the mucus layer was realized by connecting the tip of the syringe to the bottom of a vertical cylindrical vessel by a flexible tubing, filling the vessel with PBS, level with the surface of the mucus layer in the syringe, and dripping PBS into the vessel without causing any phase mixing. Although the mucoadhesive NP interact more strongly with the mucus, yet they are able to overcome this barrier with the aid of the water movement from lumen to epithelium. This new method promises to be more predictive of in vivo NP transport across the mucus than already reported methods, as it takes into account the water movement and regulates its contribution to the physiologic value.
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 33, Pisa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Fabiano
authors.affiliation: Department of Pharmacy, University of Pisa, Via Bonanno, 33, Pisa, Italy. Electronic address: ylenia.zambito@unipi.it.
authors.forename: Ylenia
authors.initials: Y
authors.lastname: Zambito
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Center for Chemistry and Biomedicine, Innrain 80/82, Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry; D004058:Diffusion; D006820:Hyaluronic Acid / Q000737:chemistry; D009093:Mucus / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012212:Rheology / Q000295:instrumentation / Q000379:methods; D012965:Sodium Chloride / Q000737:chemistry*; D013552:Swine; D014783:Viscosity
chemical_list: D012965:Sodium Chloride; D006820:Hyaluronic Acid; D048271:Chitosan
keywords: Intestinal absorption; Intestinal water movement; Mucoadhesive nanoparticles; Nanoparticles diffusion in mucus; Thiolated chitosan