title: In vitro intestinal co-culture cell model to evaluate intestinal absorption of edelfosine lipid nanoparticles.
abstract: Nanotechnology is providing a new therapeutic paradigm by enhancing drug efficacy and preventing side-effects. Edelfosine is a synthetic ether lipid analogue of platelet activating factor with high antitumor activity. The encapsulation of this potent antitumor drug in lipid nanoparticles increases its oral bioavailability; moreover, it prevents the hemolytic and gastrointestinal side-effects of the free drug. The literature points towards lymphatic absorption of lipid nanoparticles after oral administration, and previous in vitro and in vivo studies stress the protection against toxicity that these nanosystems provide. The present study is intended to assess the permeability of lipid nanoparticles across the intestinal barrier. Caco-2 monoculture and Caco-2/Raji co-culture were used as in vitro models of enterocytes and Microfold cells respectively. Results showed that free drug is internalized and possibly metabolized in enterocytes. These results do not correlate with those observed in vivo when edelfosine-lipid nanoparticles were administered orally in mice, which suggests that the microfold model is not a good model to study the absorption of edelfosine-lipid nanoparticles across the intestinal barrier in vitro.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lasa-Saracíbar
authors.forename: Melissa
authors.initials: M
authors.lastname: Guada
authors.forename: Victor
authors.initials: V
authors.lastname: Sebastián
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31080 Pamplona, Spain. mjblanco@unav.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D018920:Coculture Techniques; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D020895:Enterocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption; D008055:Lipids / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010316:Particle Size; D010742:Phospholipid Ethers / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D008055:Lipids; D010742:Phospholipid Ethers; C026659:edelfosine