title: Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug.
abstract: Oral administration of low permeable drugs remains a challenge as they do not cross biological membrane efficiently and therefore exhibit a poor bioavailability. Herein, the effect of magnetic retention on the circulation and bioavailability of magnetic beads in the gastrointestinal tract in the presence of an external magnetic field is evaluated. Retention efficiency is imaged using magnetic resonance and near infrared techniques. The effect on bioavailability is then evaluated in a pharmacokinetic study. Iron oxide nanoparticles, the drug (dipeptidyl peptidase-IV inhibitor) and a fluorophore (Alexa Fluor-750) are co-encapsulated in chitosan-alginate core-shell beads. Retention of these beads is induced by the presence of an external permanent magnet on the abdomen of rats. After single administration of magnetic beads containing 20mg/kg of drug to fasted rats, a 2.5-fold increase in drug's bioavailability is observed in the presence of an external magnetic field, significantly higher than the same dose administered to rats without the field or for the drug in aqueous solution. Retention of the magnetic carriers in the presence of an external magnet proves to accumulate these carriers in a specific localization of the intestine leading to a significant improve in the drug's bioavailability.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8234, PHENIX, F-75005, Paris, France.
authors.forename: Anjali
authors.initials: A
authors.lastname: Seth
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: David
authors.initials: D
authors.lastname: Lafargue
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Poirier
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Badier
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Delory
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Laporte
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Delbos
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Jeannin
authors.affiliation: Technologie Servier, 25/27 rue Eugène Vignat, 45000 Orléans, France.
authors.forename: Jean-Manuel
authors.initials: JM
authors.lastname: Péan
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR 8234, PHENIX, F-75005, Paris, France. Electronic address: christine.menager@upmc.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Ménager
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D065546:Drug Liberation; D005243:Feces / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D060328:Magnetic Phenomena; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D010539:Permeability; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism
chemical_list: D000464:Alginates; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004337:Drug Carriers; D006603:Hexuronic Acids; D058185:Magnetite Nanoparticles; D020723:Glucuronic Acid; D048271:Chitosan; D007501:Iron
keywords: Dual imaging; Magnetic beads; Magnetic retention; Oral delivery; Pharmacokinetic