Thiolated Glycol Chitosan Bearing α-Cyclodextrin for Sustained Delivery of PEGylated Human Growth Hormone

Abstract

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.

Keywords:

• Protein delivery
• PEG-hGH
• glycol chitosan
• α-cyclodextrin
• in situ cross-linking

Acknowledgements

This work was supported by the Conversing Research Program (20090081876) and Basic Science Research Programs (20100027955 and 20100015804) of MEST, the Korea Healthcare Technology R&D Project (A101706-1001-0000200) of MW, and the BioImaging Research Center at GIST, Republic of Korea.