Zhang Q, Ding J, Yie G, Wei S
School of Pharmaceutical Sciences, Beijing Medical University, Beijing 100083.
Yao Xue Xue Bao. 1998;33(2):152-6.
The insulin-loaded polyalkylcyanoacrylate nanoparticles (INS-NP) were made with Dextran 70 as the stabilizer. The mean diameter of INS-NP was 252.4 nm with a poly dispersity of 0.005. The associating ratio of insulin to the nanoparticles reached 70.1% +/- 2.3%, while the loading capacity was 0.14 u.mg-1. Studies on in vitro release kinetics showed that release profiles can be well modelled using a biexponential function. The burst effect was obvious, and a faster release was observed in acidic media. After various doses of INS-NP were intragastrically given to diabetic rats, significant decrease of glucose level was achieved in the 10 and 20 u.kg-1 groups, with no significant difference between these two doses. The relative bioavailability after p.o. administration of INS-NP 10 u.kg-1 over s.c. administration of insulin solution 1 u.kg-1 was 7.58% calculated by the area over the curve of glucose level (%) versus time profiles. The correlation was obvious between the % of insulin released at pH 7.0 and the % of glucose decreased within the first 7 hours. Hence, an oral insulin preparation with rather high bioavailability was provided in this study, and its shorter effective time will make it more convenient for the control of the glucose level in clinics.
以葡聚糖70作为稳定剂制备了载胰岛素聚烷基氰基丙烯酸酯纳米粒（INS-NP）。INS-NP的平均直径为252.4 nm，多分散性为0.005。胰岛素与纳米粒的结合率达到70.1%±2.3%，而载药量为0.14μg·mg⁻¹。体外释放动力学研究表明，释放曲线可用双指数函数很好地模拟。突释效应明显，在酸性介质中观察到更快的释放。给糖尿病大鼠灌胃不同剂量的INS-NP后，10和20μg·kg⁻¹组血糖水平显著降低，这两个剂量之间无显著差异。通过血糖水平（%）对时间曲线的曲线下面积计算，口服10μg·kg⁻¹的INS-NP相对于皮下注射1μg·kg⁻¹胰岛素溶液的相对生物利用度为7.58%。在pH 7.0时释放的胰岛素百分比与最初7小时内血糖降低的百分比之间相关性明显。因此，本研究提供了一种生物利用度相当高的口服胰岛素制剂，其较短的有效时间将使其在临床控制血糖水平方面更加方便。
