右旋糖酐凝胶微球偶联异烟肼的合成及其体外释放

Synthesis and release in vitro of isoniazid-dextran conjugate microsphere

文章采用醛基右旋糖酐与环氧氯丙烷反应交联制备醛基右旋糖酐凝胶微球,然后与高水溶性的异烟肼反应合成了右旋糖酐凝胶微球偶联异烟肼,借助IR、TEM和激光粒度测定仪对产物的结构进行了表征,同时,对凝胶微球偶联异烟肼的体外释放进行了研究。结果表明,醛基右旋糖酐在水中能自组装成纳米凝胶粒;氧化度16.4%的醛基右旋糖酐粒径为500 nm左右,其与环氧氯丙烷反应交联团聚成粒径为2.5μm左右的凝胶微球;该微球的醛基与异烟肼反应成腙键,偶联的右旋糖酐凝胶微球偶联异烟肼,且粒径进一步增大,并集中在6-10μm,符合肺部靶向的粒径要求;右旋糖酐微凝胶偶联异烟肼在pH=4.5的酸性体系中的释放比pH=7.4的缓冲体系中的要快得多,该偶联物是酸敏感的,pH=4.5和pH=7.4的体系中的释药动力学方程分别为Rc=100t^1.31/（24.8＋1.4t^1.21）和Rc=100t^1.67/（248.6＋4.01t^1.48）。

The novel isoniazid conjugate based on the aldehyde dextran gelatinized microsphere was prepared by crosslinking with epichlorohydrin,then condensing with isoniazid in water.The product structures were characterized with IR,TEM and laser particle size analyzer,and the conjugate release in vitro was studied.The results show that the aldehyde dextran can assemble to nanoparticle,the size of aldehyde dextran with 16.4% oxidation degree is about 500 nm in water,and the gelatinized microsphere size increases to about 2.5 μm after crosslinking;and that the microsphere couples with isoniazid via hydrazone bond while its size increases to 6-10 μm.The release rate of isoniazid from this conjugate in simulative environment of pH 4.5 acidic system is much higher than that in simulative physiological environment of pH 7.4,and their drug release processes accord with kinetics equation Rc=100t^1.31/（24.8＋1.4t^1.21） and Rc=100t1.67/（248.6＋4.01t^1.48）.Therefore,the crosslinking reaction takes place between nanogel particles,and the conjugate is acid-sensitive and in line with the targeted particle size requirement of the lung.