초록 |
Oral delivery of therapeutic peptides and proteins is one of the greatest challenges in pharmaceutical fields. When peptides and proteins are orally administered, the major problem is degradation by proteolytic enzymes and acidic environment in the gastrointestinal (GI) tract. In recent years, considerable research effort has been invested in using hydrogels to solve this problem. Especially stimuli-sensitive hydrogels have generated a significant interest in this field due to their ability to respond to environmental changes. It is known that the saccharide is one of the important constitute of living cell and plays an important role in the cell recognition process. Because of its good biocompatibility and molecular recognition, many biomaterials containing saccharide have been prepared and investigated. In addition, vinyl derivatives of saccharide can be easily copolymerized with various comonomers and their copolymers consist of a chemically and biologically stable C-C backbone and a saccharide in their side chain. Therefore, vinyl derivatives of mono- or polysaccharide are one of the potential candidates for use as monomers of polymeric hydrogels whose properties such as swelling ratio, diffusion characteristic, biocompatibility, and bioadhesion are significantly affected by the monomer composition of the hydrogel. Here, novel glucose-containing complexation hydrogels were developed by free-radical photopolymerization of methacrylic acid and 2-methacryloxyethyl glucoside using tetra(ethylene glycol) dimethacrylate as a crosslinking agent. To study the feasibility of the hydrogel as carriers for oral protein delivery, their swelling and release behavior were investigated and various structural parameters such as the number average molecular weight between crosslinks, the mesh size, and the crosslinking density were calculated as a function of pH and copolymer compositions. To elucidate the macroscopic pH-sensitive swelling behavior of the hydrogel with complexation phenomena of the polymer network at molecular level, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopic technique was used. The pH-responsive release behavior of insulin in the physiological pH range was also investigated from the hydrogels. In acidic media (pH 2.2), insulin release from the hydrogels was very slow. However, as the pH of the medium was changed to 6.5, a rapid release of insulin was observed. |