Novel method of fabricating hydroxyapatite incorporated 5-fluorouracil loaded poly (lactide-co-glycolide) microspheres

Abstract

Hydroxyapatite-incorporated PLGA-based microspheres loaded with 5-FU were prepared using the emulsification/solvent evaporation technique. The effects of hydroxyapatite-to-polymer ratio, dimethyl sulfoxide-to-dichloromethane ratio as well the effects of polymer inherent viscosity on encapsulation efficiency were investigated. The drug release rate was studied for 5 weeks in vitro in phosphate buffered solution of pH 7.4 at 37oC. Results showed that higher drug encapsulation was attained at higher hydroxyapatite-to-polymer ratio of 0.1, lower dimethyl sulfoxide-to-dichloromethane ratio of 0.05 and using a polymer with higher inherent viscosity of 0.68 dL/g. The release of drug followed a biphasic pattern with an initial burst within 4 hours of immersion in phosphate buffered saline, followed by a zero order release. Results also indicated that initial bursts could be limited to 6% with high hydroxyapatite-to-polymer ratio of 0.1. However, the presence of hydroxyapatite increased the internal porosity of the microspheres thus increasing the rate of drug release to 1.11 %/day as compared to 0.48 %/day in microspheres without hydroxyapatite.

The potential of hydroxyapatite in limiting burst release makes the incorporation of hydroxyapatite into PLGA microspheres beneficial. Through the limiting of the initial burst release phase, there is the ability of linearizing the overall drug release profile of such a drug delivery system. From the linear sustained drug release profile over the course of 5 weeks, it has underscored the fact that HA-incorporated 5-FU-loaded PLGA microparticles synthesized using this modified oil-in-water emulsion method may hold the promise to extended periods of controlled-release for the treatment of glioblastoma multiforme.