Chitosan hydrogel as a drug delivery carrier to control angiogenesis |
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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 |
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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 |
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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. |
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Keywords: | Photocrosslinkable chitosan hydrogel Angiogenesis Drug delivery carrier Controlled release |
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