Dorkoosh F A, Verhoef J C, Borchard G, Rafiee-Tehrani M, Verheijden J H M, Junginger H E
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Int J Pharm. 2002 Oct 24;247(1-2):47-55. doi: 10.1016/s0378-5173(02)00361-7.
In this in vivo study, novel delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) polymers were used to improve the intestinal absorption of insulin in healthy pigs. Six female pigs of approximately 35 kg body weight were used. A cannula was inserted into the jugular vein for blood sampling and a silicone fistula in the duodenum for administration of gelatin capsules containing the delivery systems or insulin solutions. The delivery systems consisted of two components, (1) conveyor system made of SPH and SPHC; (2) core containing insulin. The core was inserted either into the conveyor system (core inside, c.i.) or attached to the surface of conveyor system (core outside, c.o.). The following intestinal formulations were investigated: c.i., c.o. and intraduodenal (i.d.) administration of insulin solutions. Subcutaneous (s.c.) injection of insulin was also investigated for reasons of comparison. Blood samples were taken and analyzed for insulin and glucose concentrations. Relative bioavalibility values of 1.3+/-0.4 and 1.9+/-0.7% were achieved for c.o. and c.i. administrations, respectively. The bioavalibility for i.d. administration of insulin solution was 0.5+/-0.2%. These results indicate that the absorption of insulin was slightly increased using SPH/SPHC-based delivery systems. Furthermore, a large variability was observed, probably due to physiological and metabolic changes during the experiments. Blood glucose levels were slightly decreased after the c.o. and c.i administrations, whereas these levels did not decrease after i.d. administration of insulin solutions. In conclusion, SPH/SPHC-based delivery systems are able to enhance the intestinal absorption of insulin and are, therefore, considered as promising systems for peroral peptide drug delivery. However, insulin delivery from these delivery systems under in vivo have to be improved.
在这项体内研究中，基于超多孔水凝胶（SPH）和SPH复合材料（SPHC）聚合物的新型给药系统被用于提高健康猪体内胰岛素的肠道吸收。使用了6头体重约35千克的雌性猪。将一根插管插入颈静脉用于采血，并在十二指肠处插入一个硅胶瘘管用于给药含有给药系统或胰岛素溶液的明胶胶囊。给药系统由两部分组成：（1）由SPH和SPHC制成的输送系统；（2）含有胰岛素的核心部分。核心部分要么插入输送系统内部（核心在内，c.i.），要么附着在输送系统表面（核心在外，c.o.）。研究了以下肠道制剂：c.i.、c.o.以及十二指肠内（i.d.）注射胰岛素溶液。出于比较目的，还研究了皮下（s.c.）注射胰岛素的情况。采集血样并分析胰岛素和葡萄糖浓度。c.o.和c.i.给药方式的相对生物利用度值分别为1.3±0.4%和1.9±0.7%。胰岛素溶液i.d.给药的生物利用度为0.5±0.2%。这些结果表明，使用基于SPH/SPHC的给药系统可使胰岛素的吸收略有增加。此外，观察到较大的变异性，这可能是由于实验过程中的生理和代谢变化所致。c.o.和c.i.给药后血糖水平略有下降，而i.d.注射胰岛素溶液后血糖水平并未下降。总之，基于SPH/SPHC的给药系统能够增强胰岛素的肠道吸收，因此被认为是口服肽类药物给药的有前景的系统。然而，这些给药系统在体内的胰岛素递送情况还有待改善。
