title: Drug permeation across intestinal epithelial cells using porous silicon nanoparticles.
abstract: Mesoporous silicon particles hold great potential in improving the solubility of otherwise poorly soluble drugs. To effectively translate this feature into the clinic, especially via oral or parenteral administration, a thorough understanding of the interactions of the micro- and nanosized material with the physiological environment during the delivery process is required. In the present study, the behaviour of thermally oxidized porous silicon particles of different sizes interacting with Caco-2 cells (both non-differentiated and polarized monolayers) was investigated in order to establish their fate in a model of intestinal epithelial cell barrier. Particle interactions and TNF-α were measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen species and nitric oxide levels, together with transmission electron microscope images of the polarized monolayers, were assessed with both the Caco-2 cells and RAW 264.7 macrophages. The results showed a concentration and size dependent influence on cell viability and ROS-, NO- and TNF-α levels. There was no evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Finland. luis.bimbo@helsinki.fi
authors.forename: Luis M
authors.initials: LM
authors.lastname: Bimbo
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D006118:Griseofulvin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007422:Intestines / Q000166:cytology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000096:biosynthesis; D010084:Oxidation-Reduction / Q000187:drug effects; D016062:Porosity / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012825:Silicon / Q000494:pharmacology*; D012995:Solubility / Q000187:drug effects; D013696:Temperature; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006118:Griseofulvin; D012825:Silicon