Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: Ex vivo and in vivo studies
Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: Ex vivo and in vivo studies
复制标题
DOI：
10.1016/j.ijpharm.2007.12.037
复制
发表时间：
2008-05-22
影响因子：
5.8
通讯作者：
Rafiee-Tehrani, Morteza
中科院分区：
文献类型：
--
作者：
Bayat, Akbar;Dorkoosh, Farid A.;Rafiee-Tehrani, Morteza
以壳聚糖(CS)、三乙基壳聚糖(TEC)和二甲基乙基壳聚糖(DMEC)为结肠剂，采用聚电解质络合(PEC)法制备了胰岛素纳米微粒。用动态光散射法测定了纳米粒子的粒度分布、Zeta电位和多分散指数。用透射电子显微镜观察了纳米粒子的形貌。结果表明，纳米粒子带正电荷，粒径分布在170~270 nm之间，球形，表面光滑。通过测量缔合效率和纳米粒子中胰岛素的含量来确定纳米粒子中的胰岛素负载量。所有纳米粒子的胰岛素负荷量都超过了80%。体外释放研究表明，胰岛素在大鼠结肠膜上有较好的缓释作用。体外释放实验表明，季铵盐衍生物制备的纳米粒在大鼠结肠膜上的转运优于壳聚糖纳米粒。在大鼠体内的研究表明，与游离胰岛素相比，使用这些纳米粒子可以促进糖尿病大鼠对胰岛素的结肠吸收。通过降糖作用评价胰岛素在大鼠结肠中的吸收情况。(C)2008爱思唯尔B.V.保留所有权利。
The aim of the present study was to develop insulin nanoparticulate systems by using chitosan (CS), triethylchitosan (TEC) and dimethylethylchitosan (DMEC, a new quaternized derivative of chitosan) for colon delivery.The nanoparticles were prepared by the polyelectrolyte complexation (PEC) method. Particle size distribution, zeta potential and polydispersity index of the nanoparticles were determined using dynamic light scattering technique. Transmission electron microscopy (TEM) was also used to observe the morphology of the nanoparticles. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170-270 nm with spherical morphology and smooth surface structure. The amount of insulin loaded into the nanoparticles was determined by measuring the association efficiency and also the content of insulin in the nanoparticles. Insulin loading was found to be more than 80% for all of the nanoparticles. In vitro release studies showed a small burst effect at the beginning and then a sustained release characteristic for 5 h. Ex vivo investigations revealed better insulin transport across the colon membrane of rats for nanoparticles made with quaternized derivatives than those made of chitosan. In vivo studies in rats have showed enhanced colon absorption of insulin by using these nanoparticles compared to free insulin in diabetic rats. The insulin absorption from the rat's colon was evaluated by its hypoglycemic effect. (c) 2008 Elsevier B.V. All rights reserved.