Pharmacokinetic study and effectiveness evaluation of slow-release PLGA-5-fluorouracil microsphere.

PURPOSE

The aim was to develop a slow-release poly-lactic-co-glycolic acid (PLGA)-5-fluorouracil microsphere, study the pharmacokinetic characteristics as well as to evaluate the effectiveness and safety of this preparation on colorectal tumor in vivo.

METHODS

The PLGA-5-fluorouracil microsphere was prepared based on a spray-drying method, and the drug loading of 5-fluorouracil (the percentage of 5-fluorouracil content in the whole microsphere), in vitro 5-fluorouracil release profile and pharmacokinetic characteristics were carried out through high-performance liquid chromatography. The inhibiting effect on tumor growth and safety was examined using in vivo subcutaneously (s.c.) inoculated colorectal tumor models of nude mice.

RESULTS

The size of the microsphere was less than 100 μm, drug loading was 20 % and drug release time lasted as long as 30 days. Slow-release PLGA-5-fluorouracil microsphere had longer half-life time (t (1/2)), larger apparent volume of distribution (V ( d )) and smaller area under the curve (AUC) compared with 5-fluorouracil. PLGA-5-fluorouracil microsphere significantly restrained tumor growth and this effect correlated with decreased expression of vascular endothelial growth factor in tumor cells. Body weight measurement and blood analysis did not suggest significant adverse effects on the mice during the study.

CONCLUSIONS

The slow-release PLGA-5-fluorouracil microsphere developed here was suitable for regional use; it has pharmacokinetic advantages and appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.