title: A biocompatible calcium salt of hyaluronic acid grafted with polyacrylic acid.
abstract: We have synthesized hyaluronic acid (HA) grafted with polyacrylic acid (PAA) via controlled radical polymerization (CRP) in aqueous media. The grafted HA (HA-g-PAA) showed slow degradation by hyaluronidase compared with unmodified HA as a result of the steric hindrance produced by grafted PAA, and PAA was detached by hydrolysis and enzymatic degradation by lipase. It formed an insoluble salt immediately after mixing with Ca(2+) by the binding between grafted PAA and Ca(2+). Both HA-g-PAA and its salt showed good biocompatibility, especially to mesothelial cells in vitro. Finally, they were administered into mice subcutaneously and intraperitoneally. The residue of the material was observed 7 days after subcutaneous administration, while the material was almost cleared from the peritoneum 7 days after intraperitoneal administration with or without Ca(2+). HA-g-PAA is expected to be applicable to medical uses such as drug delivery in the peritoneum and for materials preventing peritoneal adhesion.
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan. Electronic address: y_nakaga@chemsys.t.u-tokyo.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: satoshinakasako@gmail.com.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakasako
authors.affiliation: Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: s-ohta@chemsys.t.u-tokyo.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan; Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address: taichi@m.u-tokyo.ac.jp.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D010537:Peritoneum / Q000187:drug effects; D012492:Salts / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D001672:Biocompatible Materials; D012492:Salts; C006903:carbopol 940; D006820:Hyaluronic Acid; D002118:Calcium
keywords: Adhesion-preventing material; Controlled radical polymerization; Drug delivery; Hyaluronic acid; Intraperitoneal administration; Polyacrylic acid