title: Chitosan hydrogel as a drug delivery carrier to control angiogenesis.
abstract: An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO(4)-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.
authors.affiliation: Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan. ishihara@ndmc.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Kiyohaya
authors.initials: K
authors.lastname: Obara
authors.forename: Singo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujita
authors.forename: Kazunori
authors.initials: K
authors.lastname: Masuoka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kanatani
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Miya
authors.initials: M
authors.lastname: Ishihara
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Maehara
authors.forename: Makoto
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009779:Occlusive Dressings; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D011817:Rabbits; D014466:Ultraviolet Rays; D014945:Wound Healing / Q000502:physiology
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D048271:Chitosan; D017239:Paclitaxel