title: LARETH-25 and β-CD improve central transitivity and central pharmacological effect of the GLP-2 peptide.
abstract: Depression is a common mental disorder. More than 350 million people of all ages suffer from depression worldwide. Although a number of antidepressants are available, >20% of patients with major depressive disorder suffer from treatment-resistant depression. Therefore, development of novel therapeutics to overcome this condition is required. We reported that intracerebroventricular administration of glucagon-like peptide-2 (GLP-2) exerts antidepressant-like effects treated with or without adrenocorticotropic hormone. In the present study, we developed a nasal formulation of GLP-2 containing 5% polyoxyethylene (25) lauryl ether and 1% β-cyclodextrin that enhanced the resistance of GLP-2 to inactivation by dipeptidyl peptidase-4. Intranasal administration of this formulation (60μg/kg) increased the delivery of GLP-2 to the brain and had antidepressant-like effects on rats. These results suggest the potential of the GLP-2 nasal formulation for use as a novel antidepressant.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Columbia University Medical Center, Postdoctoral Fellowship for Research Abroad by Japan Society for the Promotion of Science, 1130 St. Nicholas Avenue, New York, NY, 10032, USA. Electronic address: horiguchim@rs.tus.ac.jp.
authors.forename: Michiko
authors.initials: M
authors.lastname: Horiguchi
authors.affiliation: Department of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Department of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Translational Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Sasaki-Hamada
authors.affiliation: Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ozawa
authors.affiliation: Department of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Funane
authors.affiliation: Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Ozawa
authors.affiliation: Department of Pharmacology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Translational Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors.forename: Jun-Ichiro
authors.initials: JI
authors.lastname: Oka
authors.affiliation: Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan. Electronic address: chikamasa_yamashita@rs.tus.ac.jp.
authors.forename: Chikamasa
authors.initials: C
authors.lastname: Yamashita
mesh_terms: D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018819:Dipeptidyl Peptidase 4 / Q000008:administration & dosage / Q000737:chemistry; D053767:Glucagon-Like Peptide 2 / Q000008:administration & dosage* / Q000737:chemistry*; D008297:Male; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D053767:Glucagon-Like Peptide 2; D047392:beta-Cyclodextrins; D000077423:Polidocanol; D011092:Polyethylene Glycols; D018819:Dipeptidyl Peptidase 4; C031215:betadex
keywords: Brain drug delivery and targeting; Glucagon-like peptide-2; Nano micelle; Nasal formulation; Polycxyethylene (25) lauryl ether (LAURETH-25); β-cyclodextrin (β-CD)