Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug

• Published in: European journal of pharmaceutical sciences Vol. 100; pp. 25 - 35
• Main Authors: Seth, Anjali, Lafargue, David, Poirier, Cécile, Badier, Thomas, Delory, Nathalie, Laporte, Alain, Delbos, Jean-Marie, Jeannin, Véronique, Péan, Jean-Manuel, Ménager, Christine
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.03.2017; Elsevier
• Subjects: Alginates - chemistry; Animals; Biological Availability; Chitosan - chemistry; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - blood; Dipeptidyl-Peptidase IV Inhibitors - chemistry; Dipeptidyl-Peptidase IV Inhibitors - pharmacokinetics; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Liberation; Dual imaging; Feces - chemistry; Gastrointestinal Tract - metabolism; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Iron - metabolism; Life Sciences; Liver - metabolism; Magnetic beads; Magnetic Phenomena; Magnetic retention; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - chemistry; Male; Oral delivery; Permeability; Pharmaceutical sciences; Pharmacokinetic; Pharmacology; Rats, Wistar; Spleen - metabolism; Magnetic retention; Magnetic beads; Pharmacokinetic; Oral delivery; Dual imaging
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2016.12.022

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. Magnetic retention of core-shell chitosan-alginate beads containing iron oxide nanoparticles is investigated for bioavailability improvement of a low permeable drug. The efficiency of magnetic retention in the intestine is observed by Magnetic Resonance and Near Infra-red imaging. The impact on drug's bioavailability as well as the toxicity of these magnetic carriers is then studied in vivo in the gastro intestinal tract. [Display omitted]