Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth.
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.
Ishihara
Masayuki
M
Research Institute, National Defense Medical Collage, Tokorozawa, Saitama 359-8513, Japan. ishihara@ndmc.ac.jp
Fujita
Masanori
M
Obara
Kiyohaya
K
Hattori
Hidemi
H
Nakamura
Shingo
S
Nambu
Masaki
M
Kiyosawa
Tomoharu
T
Kanatani
Yasuhiro
Y
Takase
Bonpei
B
Kikuchi
Makoto
M
Maehara
Tadaaki
T
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*
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D048271:Chitosan; D017239:Paclitaxel