A novel pH- and ionic-strength-sensitive carboxy methyl dextran hydrogel.

A fast and simple method for the preparation of pH-sensitive hydrogel membranes for drug delivery and tissue engineering applications has been developed using carbodiimide chemistry. The hydrogels were formed by the intermolecular cross-linking of carboxymethyl dextran (CM-dextran) using 1-ethyl-(3-3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Infrared spectra of the hydrogels suggest the formation of ester bonds between the hydroxyl and carboxyl groups in the CM-dextran. The porosity of the hydrogels produced, as shown by protein diffusion, increases in response to changes in the pH and the ionic strength of the external medium. The results show pH-dependent swelling behaviour arising from the acidic pedant groups in the polymer network. The diffusion of the protein lysozyme through the hydrogel membranes increased with increases in both pH (5.0-9.0) and ionic strength. The effect of changes of pH and ionic strength on the hydrogel's permeability was shown to be reversible. Scanning electron microscopy of these hydrogels showed that pH-dependent changes in permeability are mirrored by morphological changes in gel structure.

[1]  Chih-Chang Chu,et al.  Synthesis and characterization of dextran-based hydrogel prepared by photocrosslinking , 1999 .

[2]  D. Mooney,et al.  Hydrogels for tissue engineering. , 2001, Chemical Reviews.

[3]  R. Eisenthal,et al.  NAD‐sensitive hydrogel for the release of macromolecules , 2004, Biotechnology and bioengineering.

[4]  W. Hennink,et al.  Synthesis, characterization, and polymerization of glycidyl methacrylate derivatized dextran , 1995 .

[5]  H. Chiu,et al.  Effects of acrylic acid on preparation and swelling properties of pH-sensitive dextran hydrogels. , 2002, Biomaterials.

[6]  Francis J. Doyle,et al.  Dynamic Behavior of Glucose-Responsive Poly(methacrylic acid-g-ethylene glycol) Hydrogels , 1997 .

[7]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery , 2001 .

[8]  G. Hsiue,et al.  Synthesis and characterization of pH-sensitive dextran hydrogels as a potential colon-specific drug delivery system. , 1999, Journal of biomaterials science. Polymer edition.

[9]  L. Brannon-Peppas,et al.  Dynamic and equilibrium swelling behaviour of pH-sensitive hydrogels containing 2-hydroxyethyl methacrylate. , 1990, Biomaterials.

[10]  H. Brøndsted,et al.  Crosslinked dextran--a new capsule material for colon targeting of drugs. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Y. Ikada,et al.  Crosslinking of hyaluronic acid with water-soluble carbodiimide. , 1997, Journal of biomedical materials research.

[12]  A. Hardikar,et al.  pH-sensitive freeze-dried chitosan-polyvinyl pyrrolidone hydrogels as controlled release system for antibiotic delivery. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[13]  Nobuhiko Yui,et al.  Double‐stimuli‐responsive degradable hydrogels: interpenetrating polymer networks consisting of gelatin and dextran with different phase separation , 1996 .

[14]  G. Amidon,et al.  pH-Dependent Swelling and Solute Diffusion Characteristics of Poly(Hydroxyethyl Methacrylate–CO–Methacrylie Acid) Hydrogels , 1988, Pharmaceutical Research.

[15]  Nicholas A. Peppas,et al.  Equilibrium swelling behavior of pH-sensitive hydrogels , 1991 .

[16]  A. Katchalsky,et al.  Polyelectrolyte gels in salt solutions , 1955 .

[17]  N. Peppas,et al.  Release behavior of bioactive agents from pH-sensitive hydrogels. , 1993, Journal of biomaterials science. Polymer edition.

[18]  Young Moo Lee,et al.  pH/temperature-responsive behaviors of semi-IPN and comb-type graft hydrogels composed of alginate and poly(N-isopropylacrylamide) , 2001 .

[19]  J. Varshosaz,et al.  The effect of structural changes on swelling kinetics of polybasic/hydrophobic pH-sensitive hydrogels. , 1998, Drug development and industrial pharmacy.

[20]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[21]  G L Amidon,et al.  A pH- and ionic strength-responsive polypeptide hydrogel: synthesis, characterization, and preliminary protein release studies. , 1999, Journal of biomedical materials research.

[22]  C. Chu,et al.  Synthesis and characterization of dextran-methacrylate hydrogels and structural study by SEM. , 2000, Journal of biomedical materials research.

[23]  A. R. Kulkarni,et al.  Chemically modified polyacrylamide-g-guar gum-based crosslinked anionic microgels as pH-sensitive drug delivery systems: preparation and characterization. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[24]  H. Brøndsted,et al.  Dextran hydrogels for colon-specific drug delivery , 1995 .

[25]  W. Hennink,et al.  Reaction of Dextran with Glycidyl Methacrylate: An Unexpected Transesterification , 1997 .

[26]  Y. Ikada,et al.  Mechanism of amide formation by carbodiimide for bioconjugation in aqueous media. , 1995, Bioconjugate chemistry.

[27]  R. Guidoin,et al.  Characteristics of polyester arterial grafts coated with albumin: the role and importance of the cross-linking chemicals. , 1988, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[28]  R. Eisenthal,et al.  A reversible hydrogel membrane for controlling the delivery of macromolecules. , 2003, Biotechnology and bioengineering.