Modeling of swelling and drug release behavior of spontaneously forming hydrogels composed of phospholipid polymers

Physically cross-linked hydrogel had been investigated in order to make use of oral polypeptide drug delivery carrier. By using 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer, we had prepared a spontaneously forming hydrogel showing controllable dissociation via pH changes. In this study, the dissociation and release of polypeptide drugs from the MPC polymer hydrogel loaded with polypeptide drugs, which had been prepared from aqueous solutions containing water-soluble poly[MPC-co-methacrylic acid (MA)] (PMA) and poly[MPC-co-n-butyl methacrylate (BMA)] (PMB) had been executed. The polymer concentration was 10 wt.% and PMA/PMB feed ratio (A/B feed ratio) was 5/5. Insulin labeled with fluorescein-4-isothiocyanate (FITC) and cytochrome c had been loaded for the examination of the release behavior. The hydrogel in pH 1.8 aqueous solution would be swelling, for the hydrogel would absorb outside water. However, during this process, the polymer is dissoluting out from the hydrogel due to the widening of the polymer network. The cytochrome c followed anomalous transport while insulin depended on the swelling and dissolution of the polymer chains. The hydrogel showed surface erosion in neutral condition, although the hydrogel is composed of two different polymer possessing divergent physical properties. The release followed anomalous transport, but the erosion rate slightly changed with as the hydrophobicity of the loaded drugs. The total amount of the drugs released in neutral condition was larger compared to the acidic condition. When the eroded percentage and the release percentage were compared with each other, it showed that release was slightly slower than erosion, indicating that the erosion was controlling the release phenomenon. (C) 2004 Elsevier B.V. All rights reserved.