Sivasubramanian Maharajan, Kim Yu-Jeong, Chae Su Young, Son Sohee, Jo Dong-Gyu, Lee Kang Choon, Yoo Chang Kyoo, Park Jae Hyung
a Department of Advanced Polymer and Fiber Materials , Kyung Hee University , Gyeonggi-do , 446-701 , South Korea.
J Biomater Sci Polym Ed. 2012;23(15):1995-2005. doi: 10.1163/092050611X603700. Epub 2012 May 8.
The extensive use of human growth hormone (hGH), emerging as protein therapeutics, has been limited by its instability in biological fluids and short biological half-life. In this study, thiolated glycol chitosan bearing α-cyclodextrin (TGC-CD), in situ cross-linked by poly(ethylene glycol)-diacrylate (PEG-DA), was synthesized to develop a sustained release system for PEGylated hGH (PEG-hGH). TGC-CD could form a stable inclusion complex with PEG-hGH by the physical interaction between the inner cavity of CD and PEG. Such a complex was readily cross-linked in the presence of PEG-DA via a Michael-type addition reaction. From the in vitro release experiments of PEG-hGH, it was confirmed that PEG-hGH was completely released from the complex for 12 h in PBS (pH 7.4), whereas the release rate of PEG-hGH was significantly reduced by the chemical cross-linking of the complex. PEG-hGH, released from the cross-linked complexes, maintained its structural integrity, which was demonstrated using circular dichroism spectroscopy. Overall, TGC-CD might be useful for sustained delivery of PEG-hGH.
作为蛋白质治疗药物，人类生长激素（hGH）的广泛应用受到其在生物流体中稳定性差和生物半衰期短的限制。在本研究中，合成了带有α-环糊精的硫醇化乙二醇壳聚糖（TGC-CD），并通过聚（乙二醇）-二丙烯酸酯（PEG-DA）进行原位交联，以开发一种用于聚乙二醇化hGH（PEG-hGH）的缓释系统。TGC-CD可以通过CD内腔与PEG之间的物理相互作用与PEG-hGH形成稳定的包合物。这种复合物在PEG-DA存在下通过迈克尔型加成反应很容易交联。从PEG-hGH的体外释放实验可知，在PBS（pH 7.4）中，PEG-hGH在12小时内从复合物中完全释放，而复合物的化学交联显著降低了PEG-hGH的释放速率。从交联复合物中释放的PEG-hGH保持了其结构完整性，这通过圆二色光谱法得到了证实。总体而言，TGC-CD可能有助于PEG-hGH的持续递送。
