Bayat Akbar, Dorkoosh Farid A, Dehpour Ahmad Reza, Moezi Leila, Larijani Bagher, Junginger Hans E, Rafiee-Tehrani Morteza
Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int J Pharm. 2008 May 22;356(1-2):259-66. doi: 10.1016/j.ijpharm.2007.12.037. Epub 2008 Jan 5.
The aim of the present study was to develop insulin nanoparticulate systems by using chitosan (CS), triethylchitosan (TEC) and dimethyl-ethylchitosan (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 5h. 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.
本研究的目的是利用壳聚糖（CS）、三乙基壳聚糖（TEC）和二甲基乙基壳聚糖（DMEC，一种新型的壳聚糖季铵化衍生物）开发用于结肠给药的胰岛素纳米颗粒系统。通过聚电解质络合（PEC）法制备纳米颗粒。使用动态光散射技术测定纳米颗粒的粒径分布、zeta电位和多分散指数。还使用透射电子显微镜（TEM）观察纳米颗粒的形态。结果发现，纳米颗粒带正电荷，粒径分布在170-270nm范围内，呈球形形态且表面结构光滑。通过测量结合效率以及纳米颗粒中胰岛素的含量来确定负载到纳米颗粒中的胰岛素量。发现所有纳米颗粒的胰岛素负载量均超过80%。体外释放研究表明，开始时有较小的突释效应，然后具有5小时的持续释放特性。离体研究表明，与壳聚糖制成的纳米颗粒相比，季铵化衍生物制成的纳米颗粒在大鼠结肠膜上的胰岛素转运效果更好。大鼠体内研究表明，与糖尿病大鼠中的游离胰岛素相比，使用这些纳米颗粒可增强胰岛素在结肠的吸收。通过其降血糖作用评估大鼠结肠对胰岛素的吸收。
