title: Optimized chemical structure of nanoparticles as carriers for oral delivery of salmon calcitonin.
abstract: Nanoparticles having two kinds of surface hydrophilic polymeric chains were prepared by the free radical copolymerization between styrene and hydrophilic macromonomers terminating in vinylbenzyl groups. Their potential as carriers for oral peptide delivery was investigated using salmon calcitonin (sCT) in rats. After oral administration of mixtures of sCT and nanoparticles, the ionized calcium concentration in blood was measured. The absorption of sCT was significantly enhanced by nanoparticles having poly-N-isopropylacrylamide (PNIPAAm) chains on their surfaces. This enhancement effect was considerably increased by introducing cationic poly-vinylamine (PVAm) groups to the surface of PNIPAAm nanoparticles. The absorption enhancement depended on the ratio of NIPAAm and VAm macromonomers to styrene in the nanoparticle preparation. In contrast, the introduction of nonionic poly-vinylacetamide (PNVA) groups eliminated completely the absorption-enhancing function of PNIPAAm nanoparticles. It was suggested that this disappearance was due to the shielding of PNIPAAm groups by PNVA groups. The enhancement effect of sCT absorption by nanoparticles was greatly dominated by their chemical structure that was closely related to surface characteristics. Optimization of the chemical structure on the basis of the mechanism of the absorption enhancement resulted in the further improvement of sCT absorption.
authors.affiliation: Drug Metabolism and Physicochemical Property Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 1-16-13, Kita-kasai, Edogawa-ku, Tokyo 134-8630, Japan. sakumv8j@daiichipharm.co.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakuma
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
authors.forename: Rika
authors.initials: R
authors.lastname: Sudo
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hiwatari
authors.forename: Akio
authors.initials: A
authors.lastname: Kishida
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000180:Acrylic Resins; D000284:Administration, Oral; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004337:Drug Carriers; D005612:Freeze Drying; D006868:Hydrolysis; D008297:Male; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; C052970:poly-N-isopropylacrylamide; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium