Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth

Curr Drug Deliv. 2006 Oct;3(4):351-8. doi: 10.2174/156720106778559047.

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.

Publication types

  • Review

MeSH terms

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

Substances

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