Chung H, Kim J, Um J Y, Kwon I C, Jeong S Y
Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea.
Diabetologia. 2002 Mar;45(3):448-51. doi: 10.1007/s00125-001-0751-z.
AIMS/HYPOTHESIS: A patient with (insulin-dependent) diabetes mellitus receives at least one subcutaneous insulin injection a day to maintain low serum glucose concentrations. Since patients' compliance with such dosage regimens is too low, the development of an oral formula is clearly attractive. We present the development of a liquid formula that can be easily dispersed in water to produce particles named "nanocubicles" which efficiently encapsulate insulin.
Fasted streptozotocin-induced diabetic rats were administered orally with particles encapsulating insulin, and particles without insulin or soluble insulin in water. Groups of rats were also injected soluble insulin in PBS for control. Blood glucose concentration and insulin concentration were measured 1, 2, 3, 4 and 6 h after the administration of the insulin formulas.
In vitro experiments show that the particles can be taken up by the Caco-2 cells at a high ratio. The serum glucose concentration was controlled for more than 6 h after oral insulin administration but returned to the basal concentration in 3 h when 1 IU/kg of insulin was injected intravenously.
CONCLUSION/INTERPRETATION: Our biocompatible and stable oral insulin formulation is easy to prepare and produces reproducible hypoglycaemic effects, therefore we anticipate clinical acceptance and utilization of this form of insulin therapy.
目的/假设：胰岛素依赖型糖尿病患者每天至少进行一次皮下胰岛素注射以维持低血清葡萄糖浓度。由于患者对这种给药方案的依从性过低，开发口服制剂显然具有吸引力。我们展示了一种液体配方的开发，该配方可轻松分散于水中以产生名为“纳米小室”的颗粒，这些颗粒能有效包裹胰岛素。
对禁食的链脲佐菌素诱导的糖尿病大鼠口服包裹胰岛素的颗粒、不含胰岛素的颗粒或水中的可溶性胰岛素。还设置了在磷酸盐缓冲盐水中注射可溶性胰岛素的大鼠组作为对照。在给予胰岛素制剂后1、2、3、4和6小时测量血糖浓度和胰岛素浓度。
体外实验表明，这些颗粒能被Caco-2细胞大量摄取。口服胰岛素后，血清葡萄糖浓度在6小时以上得到控制，但静脉注射1 IU/kg胰岛素时，血糖浓度在3小时后恢复到基础浓度。
结论/解读：我们的生物相容性良好且稳定的口服胰岛素制剂易于制备，并能产生可重复的降血糖作用，因此我们预计这种胰岛素治疗形式会被临床接受并得到应用。
