title: 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.
authors: a Department of Advanced Polymer and Fiber Materials , Kyung Hee University , Gyeonggi-do , 446-701 , South Korea.
authors: Maharajan
authors: M
authors: Sivasubramanian
authors: Yu-Jeong
authors: YJ
authors: Kim
authors: Su Young
authors: SY
authors: Chae
authors: Sohee
authors: S
authors: Son
authors: Dong-Gyu
authors: DG
authors: Jo
authors: Kang Choon
authors: KC
authors: Lee
authors: Chang Kyoo
authors: CK
authors: Yoo
authors: Jae Hyung
authors: JH
authors: Park
mesh_terms: D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry; D002942:Circular Dichroism; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D065546:Drug Liberation; D006728:Hormones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D006728:Hormones; D047391:alpha-Cyclodextrins; C118638:glycol-chitosan; C437167:poly(ethylene glycol)diacrylate; D019382:Human Growth Hormone; D011092:Polyethylene Glycols; D048271:Chitosan; C032613:alpha-cyclodextrin