title: Dependence of Intestinal Absorption Profile of Insulin on Carrier Morphology Composed of β-Cyclodextrin-Grafted Chitosan.
abstract: The effect of carrier morphology on the intestinal absorption of insulin was investigated using a morphology-tunable polymeric carrier, β-cyclodextrin-grafted chitosan (BCC). The insulin-BCC complexes were prepared in either acetate or citrate buffer solutions, followed by dilution with phosphate buffer for the administration. The complex had a molecular network structure in the acetate buffer, whereas nanoparticles formed in the citrate buffer. The network structure in the acetate buffer was maintained even after dilution with a phosphate buffer, but the nanoparticles in the citrate buffer caused aggregation after dilution. Both complexes enhanced the intestinal absorption of insulin. Interestingly, their absorption profiles were totally different; prompt absorption was observed for the complex prepared in acetate buffer, whereas sustained absorption was observed for the complex prepared in citrate buffer. The difference in the absorption patterns was attributed to the difference in the complex morphology. Next, penetratin, a cell-penetrating peptide, was grafted to BCC to find further improvement in the absorption behavior. A simple mixture of penetratin and BCC was also effective. An oral administration study was also conducted in mice to observe effective suppression of glucose levels, which was further enhanced by coadministration of penetratin. Thus, BCC was proven to be an effective carrier for enhancing oral absorption of peptide drugs, and it is suggested that the carrier morphology is also an important factor that influences the absorption profile.
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.|Department of Pure and Applied Chemistry, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Daimon
authors.affiliation: Faculty of Pharmaceutical Sciences, Kobe Gakuin University , 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kamei
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Kohsaku
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Faculty of Pharmaceutical Sciences, Kobe Gakuin University , 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Takeda-Morishita
authors.affiliation: Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University , 4-101 Koyama-Minami, Tottori 680-8552, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Izawa
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.|Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shoumachi, Tokushima 770-8505, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takechi-Haraya
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shoumachi, Tokushima 770-8505, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Pure and Applied Chemistry, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Pure and Applied Chemistry, Tokyo University of Science , 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Abe
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science , 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ariga
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002352:Carrier Proteins / Q000008:administration & dosage* / Q000737:chemistry; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D047392:beta-Cyclodextrins; C571277:chitosan-beta-cyclodextrin; D048271:Chitosan; C414409:penetratin
keywords: carrier morphology; cell penetrating peptide; chitosan; cyclodextrin; insulin; oral absorption