Dorkoosh Farid A, Coos Verhoef J, Ambagts Matheus H C, Rafiee-Tehrani Morteza, Borchard Gerrit, Junginger Hans E
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, The Netherlands.
Eur J Pharm Sci. 2002 Jun;15(5):433-9. doi: 10.1016/s0928-0987(02)00028-3.
Novel peroral peptide drug delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) have recently been developed in our laboratory. In this report the following issues were studied: release of the peptide drugs buserelin, octreotide and insulin from SPH and SPHC polymers and the developed delivery systems, stability of these peptides during the release and the integrity of insulin in the polymeric matrix of SPHC. Release studies from SPH and SPHC polymers revealed that buserelin, octreotide and insulin were released almost completely from the polymers. Peptide release rates from SPH were faster than from SPHC, due to the more porous structure of SPH polymer. All peptides studied in contact with SPHC polymer were stable under different environmental conditions (ambient temperature, 37 degrees C, light and darkness and at pH values 3.2 and 7.2). FTIR studies demonstrated that no covalent binding occurred between insulin and the polymeric SPHC matrix. Release profiles of all peptides from the developed delivery systems showed a time-controlled release profile: after a short lag time of 10-15 min, a burst release of peptides occurred during which more than 80% of peptide was released within 30-45 min. In conclusion, the present delivery systems based on SPH and SPHC show appropriate in vitro properties for application in peroral peptide drug delivery of buserelin, octreotide and insulin, and are therefore promising for further in vivo evaluation.
我们实验室最近开发了基于超多孔水凝胶（SPH）和SPH复合材料（SPHC）的新型口服肽药物递送系统。在本报告中，研究了以下问题：肽药物布舍瑞林、奥曲肽和胰岛素从SPH和SPHC聚合物以及所开发的递送系统中的释放情况，这些肽在释放过程中的稳定性以及胰岛素在SPHC聚合物基质中的完整性。从SPH和SPHC聚合物进行的释放研究表明，布舍瑞林、奥曲肽和胰岛素几乎完全从聚合物中释放出来。由于SPH聚合物的多孔结构更多，SPH的肽释放速率比SPHC更快。与SPHC聚合物接触研究的所有肽在不同环境条件下（环境温度、37摄氏度、光照和黑暗以及pH值为3.2和7.2）均稳定。傅里叶变换红外光谱研究表明，胰岛素与聚合物SPHC基质之间未发生共价结合。所有肽从所开发的递送系统中的释放曲线显示出时间控制的释放曲线：在10 - 15分钟的短暂滞后时间后，出现肽的突释，在此期间超过80%的肽在30 - 45分钟内释放。总之，基于SPH和SPHC的当前递送系统在布舍瑞林、奥曲肽和胰岛素的口服肽药物递送应用中显示出合适的体外性质，因此有望进行进一步的体内评估。
