title: pH-modulated release of insulin entrapped in a spontaneously formed hydrogel system composed of two water-soluble phospholipid polymers.
abstract: To develop a polypeptide drug carrier through oral administration, a polymer hydrogel has been found that is very easy to prepare by mixing two water-soluble phospholipid polymers. The polymers having 2-methacryloyloxyethyl phosphorylcholine (MPC) moieties spontaneously formed a hydrogel, which showed controllable dissociation via pH changes. In this study, the MPC polymer hydrogel was prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB), and the applicability of the hydrogel as an oral drug delivery carrier was examined. The gelation process from the two MPC polymers is spontaneous, requiring no chemical reactions and/or no physical stimuli. PMB has a hydrophobic domain, which is suitable for loading hydrophobic drugs. Insulin could be very easily loaded to almost 100% in the hydrogel. PMA also has carboxyl groups, which are well known for pH sensitivity. At pH 1.8, the swelling continued for 8 h, with complete dissociation after 16 h. At pH 6.8, the hydrogel completely dissociated within 4 h. The hydrogel remained stable at pH 1.8 and released all the insulin at pH 6.8. The release rate was approximately four times faster at pH 6.8. After release, the insulin did not show any denaturing tendency.
authors.affiliation: Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Kwang Woo
authors.initials: KW
authors.lastname: Nam
authors.forename: Junji
authors.initials: J
authors.lastname: Watanabe
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishihara
mesh_terms: D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry* / Q000592:standards / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D010743:Phospholipids; D011108:Polymers; D017433:Protein Structure, Secondary; D012995:Solubility
chemical_list: D020100:Hydrogels; D007328:Insulin; D010743:Phospholipids; D011108:Polymers