title: In vivo study of the mucus-permeating properties of PEG-coated nanoparticles following oral administration.
abstract: The aim of this work was to investigate the mucus-permeating properties of poly(ethyleneglycol)-coated nanoparticles prepared from the copolymer of methyl vinyl ether and maleic anhydride (Gantrez® AN) after oral administration in rats. Nanoparticles were "decorated" with PEGs of different molecular masses (PEG2000, PEG6000 and PEG10000) at a PEG-to-polymer ratio of 0.125. All the PEG-coated nanoparticles displayed a mean size of ∼150 nm, slightly negative ζ values and a "brush" conformation as determined from the calculation of the PEG density. For in vivo studies, nanoparticles were labelled with either (99m)Tc or fluorescent tags. Naked nanoparticles displayed a higher ability to interact with the mucosa of the stomach than with the small intestine. However, these interactions were restricted to the mucus layer covering the epithelial surface, as visualised by fluorescence microscopy. On the contrary, PEG-coated nanoparticles moved rapidly to the intestine, as determined by imaging, and, then, were capable to develop important interactions with the mucosa, reaching the surface of the epithelium. These mucus permeating properties were more intense for nanoparticles coated with PEG2000 or PEG6000 than with PEG10000. However, the capability of nanocarriers to develop adhesive interactions within the mucosa decreased when prepared at excessive PEG densities.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Inchaurraga
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
authors.forename: Nekane
authors.initials: N
authors.lastname: Martín-Arbella
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Zabaleta
authors.affiliation: Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Quincoces
authors.affiliation: Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Peñuelas
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain. Electronic address: jmirache@unav.es.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Irache
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008298:Maleates / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004337:Drug Carriers; D008298:Maleates; D011095:Polyethylenes; D011092:Polyethylene Glycols; C043105:poly(methyl vinyl ether-co-maleic anhydride)
keywords: Mucosa; Mucus; Nanoparticles; Oral; Poly(ethyleneglycol); Poly(methyl vinyl ether-co-maleic anhydride)