pH-敏感介孔膦酸锆材料对胰岛素的吸附与结肠定位释放

The Adsorption and Colon--Specific Release of Ph--Sensitive Mesoporous Zirconium Diphosphonate for Insulin

本文利用ξ电势系统地研究了pH-敏感介孔膦酸锆材料作为载体对胰岛素的担载和释放机制。pH-敏感的介孔膦酸锆材料在不同pH值条件下的（电势证实该种材料具有可逆的阳离子骨架性质和中性表面性质，这源自于材料骨架中哌嗪基团在不同pH值条件下的质子化和去质子化作用。在pH=6．6的条件下，具有阳离子骨架性质的pH-敏感介孔膦酸锆材料通过强烈的静电吸引作用吸附负电性的胰岛素，FT-承结果表明被担载后的胰岛素仍然能够很好地保持其活性空间构型。而在pH=7．5的生理条件下，中性表面性质的pH-敏感介孔膦酸锆材料会自由地释放出负电性的胰岛素，胰岛素在结肠的释放量占胰岛素全部释放量的60％以上。这使得pH-敏感介孔膦酸锆材料有望成为胰岛素的有效载体被用于胰岛素的口服结肠给药。

The mechanism of insulin adsorbed into and released from pH--sensitive mesopomus zirconium diphosphonate as carrier was investigated in details through t; potential. The ξ potential of pH--sensitive mesoporous zirconium diphosphonate under different pH values demonstrate the materials possess reversible cationic frameworks and neutral surfaces, derived from reversible protonation--deprotonation of piperazine groups in the mesoporous walls under different pH values. At pH = 6. 6, pH--sensitive mesoporous zirconium diphosphonate with cationic frameworks adsorbed negative charged insulin through strong electrostatic attraction interactions. FT-- IR shows the insulin adsorbed into pH -- sensitive mesoporous zirconium diphosphonate can still retain its bioactive conformation. While at physiological pH value of 7. 5, pH--sensitive mesoporous zirconium diphosphonate loading insulin freely released insulin without electro- static repulsion interactions between the carrier with netural surfaces and negative charged insulin. The accumulated release profiles indicated that above 60 M of the released insulin amount can be specificly released in colon. Thus, pH--sensitive mesoporous zirconium diphosphonate might be a promising carrier for orally administrated insulin in color.