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: Masayuki Ishihara, Masanori Fujita, Kiyohaya Obara, Hidemi Hattori, Shingo Nakamura, Masaki Nambu, Tomoharu Kiyosawa, Yasuhiro Kanatani, Bonpei Takase, Makoto Kikuchi, Tadaaki Maehara
• Journal: Current drug delivery (Curr Drug Deliv) Vol. 3 Issue 4 Pg. 351-8 (Oct 2006) ISSN: 1567-2018 [Print] United Arab Emirates
• PMID: 17076636 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents, Phytogenic
• Delayed-Action Preparations
• Drug Carriers
• Hydrogels
• Fibroblast Growth Factor 2
• Chitosan
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology, therapeutic use)
• Chitosan (chemistry)
• Delayed-Action Preparations
• Drug Carriers (chemistry)
• Fibroblast Growth Factor 2 (chemistry, pharmacology, therapeutic use)
• Hydrogels (chemistry)
• Neoplasms, Experimental (drug therapy)
• Neovascularization, Physiologic (drug effects)
• Paclitaxel (chemistry, pharmacology, therapeutic use)
• Wound Healing (drug effects)