title: Improved sustained release of antigen from immunostimulatory DNA hydrogel by electrostatic interaction with chitosan.
abstract: Immunostimulatory DNA hydrogel (sDNA hydrogel) containing unmethylated cytosine-phosphate-guanine (CpG) sequences has been demonstrated to be a useful antigen delivery system, which can effectively induce an antigen-specific immune response through stimulation of the innate immune system. However, relatively rapid release of antigens from the sDNA hydrogel limits its potential. To enhance the potency of the sDNA hydrogel via improvement of its sustained release property, we selected chitosan, a biocompatible cationic polymer which electrostatically interacts with DNA, and mixed it with the sDNA hydrogel. Compared to unmixed sDNA hydrogel, sDNA hydrogel mixed with chitosan (Chitosan-sDNA hydrogel) was more stable, tougher, had more bound water, released a model antigen ovalbumin (OVA) more slowly in vitro, and provided longer retention of OVA at the injection site after intradermal injection into mice. Intradermal immunization of mice with the OVA-loaded Chitosan-sDNA hydrogel resulted in the induction of a higher level of OVA-specific IgG in serum compared with OVA-loaded sDNA hydrogel with no chitosan. These results indicate that the Chitosan-sDNA hydrogel is an improved sustained release formulation for efficient induction of antigen-specific immune responses.
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Ishii-Mizuno
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Umeki
authors.affiliation: Department of Pharmaceutical Technology, Graduate School of Medical and Pharmaceutical Science, University of Toyama, Sugitani 2630, Toyama-shi, Toyama 930-0194, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Onuki
authors.affiliation: Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.affiliation: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: makiya@pharm.kyoto-u.ac.jp.
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology; D003692:Delayed-Action Preparations; D020100:Hydrogels; D007113:Immunity, Innate / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D007271:Injections, Intradermal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D055672:Static Electricity; D013997:Time Factors
chemical_list: D000941:Antigens; D003692:Delayed-Action Preparations; D020100:Hydrogels; D007074:Immunoglobulin G; D010047:Ovalbumin; D004247:DNA; D048271:Chitosan
keywords: Antigen delivery; Chitosan; Controlled release; CpG motif; Electrostatic interaction; Hydrogel