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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 2 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 20 mg/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.
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Anjali Seth, David Lafargue, Cécile Poirier, Thomas Badier, Nathalie Delory, et al.. Optimization of magnetic retention in the gastrointestinal tract: Enhanced bioavailability of poorly permeable drug. European Journal of Pharmaceutical Sciences, Elsevier, 2016, ⟨10.1016/j.ejps.2016.12.022⟩. ⟨hal-01427399⟩

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