Morphology and size control of gelatin/hyaluronic acid composite microsphere for drug delivery

Abstract

Composite microspheres based on gelatin (Gel) and hyaluronic acid (HA) were prepared by an emulsion–coagulation method with glutaraldehyde as a crosslinker. The influences of stirring speed, crosslinker concentration, HA content and water/oil ratio on the particle size and surface morphology were investigated. The Fourier transform infrared spectra characterisation indicated that Gel and HA were crosslinked successfully by the glutaraldehyde. The in vitro release behaviours of 5-fluorouracil (5-FU) from Gel/HA microspheres were also studied. The results showed that the adhesion and agglomeration phenomena were apparent when the HA content reached 10.0 wt-%. The particle diameter of the microspheres decreased greatly with increasing stirring speed; however, the adhesion of smaller microspheres could be observed when the stirring speed reached 800 rev min^− 1. The effect of crosslinker concentration on the particle size was not significant, but the dispersion degree of the Gel/HA microspheres decreased with decreasing crosslinker content. The particle size of the microspheres gradually became uniform with the increase of the water/oil ratios. The dispersion and surface smoothness level could be improved by optimising the experimental conditions. The cumulative drug release of 5-FU from the microspheres decreased with increasing glutaraldehyde content. The results of 5-FU release kinetics from Gel/HA microspheres indicated Fickian diffusion.

Keywords:

• Gelatin
• Hyaluronic acid
• Composite microspheres
• Particle size
• Morphology
• Drug release

Acknowledgements

This work was financially supported by the National Natural Science Fund of China [grant numbers 51273062 and 51443002], the Hunan Provincial Natural Science Fund of China [grant numbers 12JJA003 and 13JJA004] and the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province.