title: Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth.
abstract: A photocrosslinkable chitosan (Az-CH-LA) aqueous solution resulted in an insoluble hydrogel like a soft rubber within 30 sec of ultraviolet light (UV)-irradiation. The photocrosslinked chitosan hydrogel showed strong sealing strength and potential use as a new tissue adhesive in surgical application. Paclitaxel, which is an anti-tumor reagent and a vascularization-inhibitor, retained in the photocrosslinked chitosan hydrogel, and were gradually released from the photocrosslinked chitosan hydrogel in vivo upon the degradation of the hydrogel. The paclitaxel-incorporated photocrosslinked chitosan hydrogels effectively inhibited tumor growth and angiogenesis in mice. On the other hand, the fibroblast growth factor (FGF)-2 molecules also retained in both the photocrosslinked chitosan and an injectable chitosan/IO(4)-heparin hydrogels, and were gradually released from the hydrogels upon their in vivo biodegradations. The activity of FGF-2 in the hydrogels was stable for long time (more than 14 days). The controlled release of biologically active FGF-2 molecules from the hydrogels caused an induction of the angiogenesis and, possibly, collateral circulation occurred in the healing-impaired diabetic (db/db) mice and the ischemic limbs of rats. The purpose of this review is to describe the effectiveness of the chitosan hydrogels (photocrosslinkable chitosan hydrogel and chitosan/IO(4)-heparin hydrogel) as a local drug delivery carrier for FGF-2 and paclitaxel to control wound repair, tumor growth, and angiogenesis. It is thus proposed that the chitosan hydrogels may be a promising new local carrier for drugs such as FGF-2 and paclitaxel.
authors.affiliation: Research Institute, National Defense Medical Collage, Tokorozawa, Saitama 359-8513, Japan. ishihara@ndmc.ac.jp
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujita
authors.forename: Kiyohaya
authors.initials: K
authors.lastname: Obara
authors.forename: Hidemi
authors.initials: H
authors.lastname: Hattori
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Nambu
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Kiyosawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kanatani
authors.forename: Bonpei
authors.initials: B
authors.lastname: Takase
authors.forename: Makoto
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Maehara
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D020100:Hydrogels / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D048271:Chitosan; D017239:Paclitaxel