title: Lipid nanoparticles enhance the absorption of cyclosporine A through the gastrointestinal barrier: In vitro and in vivo studies.
abstract: In the present work, the feasibility of cyclosporine A lipid nanoparticles (CsA LN) for oral administration was investigated. Three CsA LN formulations were developed using Precirol as lipid matrix, one stabilized with Tween(®) 80 (Tw) and the other two with mixtures of phosphatidylcholine or Pluronic(®) F127 with taurocholate (Lec:TC and PL:TC, respectively). The physical characteristics of the LN were studied under gastrointestinal pH and their integrity was found to be dependent on the stabilizers. The in vitro intestinal permeability was assessed with a human colon adenocarcinoma cell model and in vivo pharmacokinetic and biodistribution studies were performed in Balb/c mice using Sandimmune Neoral(®) as reference. In vitro results showed the highest CsA permeability with the LN containing Lec:TC. In contrast, the best in vivo performance was achieved from the LN containing Tw. The bioavailability of CsA was matched and even enhanced with Precirol nanoparticles. This study suggests the suitability of LN as promising vehicles for CsA oral delivery.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, C/Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Melissa
authors.initials: M
authors.lastname: Guada
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lasa-Saracíbar
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Hugo
authors.initials: H
authors.lastname: Lana
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain.
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Dios-Viéitez
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, C/Irunlarrea 3, E-31008 Pamplona, Spain. Electronic address: mjblanco@unav.es.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Blanco-Prieto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D016572:Cyclosporine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004075:Diglycerides / Q000737:chemistry; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D013656:Taurocholic Acid / Q000737:chemistry
chemical_list: D004075:Diglycerides; D007166:Immunosuppressive Agents; D010713:Phosphatidylcholines; D011136:Polysorbates; D020442:Poloxamer; D013656:Taurocholic Acid; D016572:Cyclosporine; C009032:precirol
keywords: Bioavailability; Caco-2 cells; Cyclosporine A; Gastrointestinal stability; Lipid nanoparticles; Oral route; Tissue distribution