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.
Subject(s)
Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/pharmacokinetics , Drug Carriers/administration & dosage , Drug Carriers/pharmacokinetics , Gastrointestinal Tract/metabolism , Magnetite Nanoparticles/administration & dosage , Alginates/chemistry , Animals , Biological Availability , Chitosan/chemistry , Dipeptidyl-Peptidase IV Inhibitors/blood , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Drug Carriers/chemistry , Drug Liberation , Feces/chemistry , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Iron/metabolism , Liver/metabolism , Magnetic Phenomena , Magnetite Nanoparticles/chemistry , Male , Permeability , Rats, Wistar , Spleen/metabolismABSTRACT
BACKGROUND: Cluster headache remains substantially underdiagnosed and undertreated. Early neurologic referral is indicated in patients with a suspected diagnosis of cluster headache (CH) so that management can be optimized and unnecessary procedures avoided. OBJECTIVE: To validate a brief self-administered questionnaire designed to screen CH cases in tertiary centers. METHODS: The review of clinical studies led us to identify the 3 more prevalent criteria of the second edition of the International Headache Society classification (International Classification of Headache Disorders, 2nd edition [ICHD II]) for all forms of CH (episodic and chronic forms). These 3 criteria were: strictly unilaterality of pain, attack duration <180 minutes if untreated, ipsilateral conjunctival injection, and/or lacrimation. These criteria were transformed in questions formulated in such a way that they could be self-administered and easily understood. Answer to each question was yes or no. Patients were unaided. The self-questionnaire was compared with the gold standard, the ICHD II criteria used by specialists at the university of Bordeaux headache center.We calculated the sensitivity and specificity for the 3 questions and for each pair of questions. RESULTS: The self-questionnaire was consecutively and prospectively submitted to 37 patients with CH and 59 patients with migraine. The 3-item questionnaire had a 78.4% sensibility and a 100% specificity. The 2-item questionnaire only using the attack duration associated with conjunctival injection and/or lacrimation was more sensitive (81.1%) with the same specificity (100%). CONCLUSIONS: This 2-item questionnaire could be a useful tool for screening CH cases in tertiary centers.
