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Chitosan hydrogel as a drug delivery carrier to control angiogenesis
Authors:Masayuki Ishihara PhD  Kiyohaya Obara MD  Singo Nakamura PhD  Masanori Fujita MD   PhD  Kazunori Masuoka MD  Yasuhiro Kanatani MD   PhD  Bonpei Takase MD   PhD  Hidemi Hattori PhD  Yuji Morimoto MD   PhD  Miya Ishihara PhD  Tadaaki Maehara MD   PhD  Makoto Kikuchi PhD
Affiliation:(1) Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan;(2) Second Department of Surgery, National Defense Medical College, Tokorozawa, Japan;(3) Department of Medical Engineering, National Defense Medical College, Tokorozawa, Japan;(4) Department of Orthopaedic Surgery, National Defense Medical College, Tokorozawa, Japan
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/IO4-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.
Keywords:Photocrosslinkable chitosan hydrogel  Angiogenesis  Drug delivery carrier  Controlled release
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