The characteristics of spontaneously forming physically cross-linked hydrogels composed of two water-soluble phospholipid polymers for oral drug delivery carrier I: hydrogel dissolution and insulin release under neutral pH condition.
Hydrogels bearing a phospholipid polar group, 2-methacryloyloxyethyl phosphorylcholine (MPC), were prepared from two aqueous solutions of polymers, water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB). The hydrogel, which was formed by physical cross-linking spontaneously without any chemical reactions and/or any physical stimuli, showed a controllable insulin release through a pH change in the medium by changing the hydrogen bonds. In this study, the mechanical strength, erosion of the hydrogel caused by polymer dissociation, and the release of insulin were examined with attention to the following three parameters of the MPC polymer: molecular weight of the polymers, composition of PMA and PMB (PMA/PMB ratio), and polymer concentration inside the hydrogel. The hydrogel with the highest mechanical strength was obtained at a PMA/PMB ratio = 3/7 (v/v, by volume ratio) while the hydrogel with the slowest dissolution was obtained at a ratio of 5/5 (v/v). The release was in good match with the dissolution and followed anomalous transport for all, but the diffusion exponent n changed according to the PMA/PMB ratio. An increase in the polymer concentration inside the hydrogel caused an increase in the mechanical strength of the hydrogel. When the polymer concentration was more than 20 wt.%, the absorption of water under neutral pH condition (pH 6.8) was observed. The release of insulin was suppressed below 10% during the swelling process of the hydrogel under neutral pH condition, while release was accelerated during the erosion process of the hydrogel. The relationship between erosion of the hydrogel and the release of the insulin depended on the erosion process of the hydrogel but differed according to the PMA/PMB ratio.
Nam
Kwangwoo
K
Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Watanabe
Junji
J
Ishihara
Kazuhiko
K
D000284:Administration, Oral; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry*; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D013997:Time Factors; D014867:Water
D003432:Cross-Linking Reagents; D004337:Drug Carriers; D020100:Hydrogels; D007328:Insulin; D008689:Methacrylates; D011109:Polymethacrylic Acids; C500651:poly(MPC-co-MA); D014867:Water; D010767:Phosphorylcholine; C079200:poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)