title: Synthesis and in vitro degradation of new polyvalent hydrazide cross-linked hydrogels of hyaluronic acid.
abstract: New polyvalent hydrazide cross-linkers were synthesized, characterized, and used to prepare hydrazide cross-linked hydrogels derived from hyaluronic acid (HA). First, the chemical synthesis and characterization of the di-, tri-, tetra-, penta-, and hexahydrazides are presented. Second, HA concentration, buffer type and concentration, and ratio of HA to carbodiimide to cross-linker were varied to obtain HA-hydrogels with different chemical and physical properties. Third, two new assays are described to monitor the stability of HA-hydrogels toward hyaluronidase (HAse) and other media. These assays were used to evaluate the stability of cross-linked HA-hydrogels to HAse solutions and different pH values. Hydrophobic cross-linkers gave the most stable gels, and the susceptibility of the gels to HAse was independent of cross-linker concentration. HAse does not significantly penetrate the HA-hydrogels and acts primarily at the gel-solution interface. The HA-hydrogels are stable in acid environments and dissolve gradually above pH 7.0.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112-5820, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Vercruysse
authors.forename: D M
authors.initials: DM
authors.lastname: Marecak
authors.forename: J F
authors.initials: JF
authors.lastname: Marecek
authors.forename: G D
authors.initials: GD
authors.lastname: Prestwich
mesh_terms: D001711:Biotransformation; D002240:Carbohydrate Sequence; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D006820:Hyaluronic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D005782:Gels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase