title: Self-gelling hydrogels based on oppositely charged dextran microspheres.
abstract: This paper presents a novel self-gelling hydrogel potentially suitable for controlled drug delivery and tissue engineering. The macroscopic gels are obtained by mixing dispersions of oppositely charged crosslinked dextran microspheres. These microspheres in turn were prepared by crosslinking of dextran derivatized with hydroxyethyl methacrylate emulsified in an aqueous poly(ethylene glycol) solution. Negatively or positively charged microspheres were obtained by addition of methacrylic acid (MAA) or dimethylaminoethyl methacrylate (DMAEMA) to the polymerization mixture. Rheological analysis showed that instantaneous gelation occurred when equal volumes of oppositely charged microspheres, dispersed in buffer solutions of pH 7, were mixed. The shear modulus of the networks could be tailored from 30 to 6500 Pa by varying the water content of the system. Moreover, controlled strain and creep experiments showed that the formed networks were mainly elastic. Importantly for application of these systems, e.g. as controlled matrix of pharmaceutically active proteins, it was demonstrated that the hydrogel system has a reversible yield point, meaning that above a certain applied stress, the system starts to flow, whereas when the stress is removed, gel formation occurred. Further it was shown that the network structure could be broken by either a low pH or a high ionic strength of the medium. This demonstrates that the networks, formed at pH 7 and at low ionic strength, are held together by ionic interactions between the oppositely charged dextran microspheres. This system holds promise as injectable gels that are suitable for drug delivery and tissue engineering applications.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), University Utrecht, Sorbonnelaan 16, P.O. Box 800082, 3508 TB, Utrecht, The Netherlands.
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Van Tomme
authors.forename: Mies J
authors.initials: MJ
authors.lastname: van Steenbergen
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D003911:Dextrans / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D004548:Elasticity; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007267:Injections; D008422:Materials Testing; D008863:Microspheres; D023822:Tissue Engineering / Q000379:methods*; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D003911:Dextrans; D020100:Hydrogels