title: PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release.
abstract: Thermosensitive polymer hydrogels that undergo a sol-to-gel transition in response to temperature changes are of great interest in therapeutic delivery and tissue engineering as injectable depot systems. A chitosan-based, injectable thermogel was prepared by grafting an appropriate amount of PEG onto the chitosan backbone and studied for drug release in vitro using bovine serum albumin (BSA) as a model protein. When more than approximately 40 wt.% of PEG was grafted to chitosan chains via covalent bonding, the aqueous solution of the resultant copolymer was an injectable liquid at low temperature and transformed to a semisolid hydrogel at body temperature. After an initial burst release in the first 5 h, a steady linear release of protein from the hydrogel was achieved for a period of approximately 70 h. Prolonged quasi-linear release of protein up to 40 days was achieved by crosslinking the hydrogel with genipin in situ, in a fashion suitable for protein encapsulation while maintaining the injectability of the hydrogel. The crosslinkage transformed the copolymer from a physical gel to an insoluble chemical gel and substantially reduced the initial burst release of protein. Both high performance liquid chromatography (HPLC) and gel electrophoresis indicated that the primary structure of BSA released from the hydrogels with or without genipin-crosslinking was generally conserved. The hydrogel can be prepared in solutions with a physiological pH, allowing the safe incorporation of bioactive molecules for a broad range of medical applications, particularly for sustained in vivo drug release and tissue engineering.
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Narayan
authors.initials: N
authors.lastname: Bhattarai
authors.forename: Hassna R
authors.initials: HR
authors.lastname: Ramay
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gunn
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Matsen
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004591:Electrophoresis, Polyacrylamide Gel; D005079:Excipients; D005612:Freeze Drying; D006358:Hot Temperature; D020100:Hydrogels / Q000737:chemistry*; D057889:Iridoid Glycosides; D039823:Iridoids; D008855:Microscopy, Electron, Scanning; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry; D012710:Serum Albumin, Bovine; D017550:Spectroscopy, Fourier Transform Infrared; D014783:Viscosity
chemical_list: D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005079:Excipients; D020100:Hydrogels; D057889:Iridoid Glycosides; D039823:Iridoids; D011506:Proteins; D011714:Pyrans; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D048271:Chitosan; C007834:genipin