Physicochemical, Morphological and Therapeutic Evaluation of Agarose Hydrogel Particles as a Reservoir for Basic Fibroblast Growth Factor

Abstract

Micron-sized agarose hydrogel particles were prepared using an emulsification/gelation method as a controlled release reservoir for basic fibroblast growth factor (bFGF). Mean particle size of agarose hydrogel particles decreased with an increase in stirring speed and also with an increasing temperature of the oil phase, as measured before cooling. Morphologies of agarose particles before and after dispersing into water were investigated by scanning electron microscopy (SEM) and cryogenic SEM, respectively. Freeze-dried agarose particles were spherical with rough surface. Porous polymer matrix structure was observed in the hydrogel particles by cryo-SEM. More than 99% of bFGF was encapsulated and the release from the agarose hydrogel particles was less than 3% during the incubation in phosphate buffered saline. bFGF molecules were not only adsorbed on the particle surface but also permeated and retained within the matrix. The therapeutic efficacy of bFGF retained in agarose hydrogel particles was significantly higher than that dissolved in saline. Agarose hydrogel particle seems to be a potential candidate for a bFGF reservoir.

Keywords:

• agarose
• basic fibroblast growth factor
• hydrogel particle
• particle size
• angiogenesis

ACKNOWLEDGMENTS

The authors greatly appreciate to Dr Takehisa Hanawa and Miss Chikako Tsuchiya at Yamanashi University for instruction of viscosity measurement. Suggestion and comments by Dr Shigeki Hijikata at Kaken Pharmaceutical Co. Ltd. are very helpful for in vitro and in vivo experiments using bFGF.