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摘要
5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0: 10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0: 10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%+/- 0.5%) and production yield (74.2%+/- 0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC]((0-t)): 12.53 +/- 1.65 mg/L*h vs 7.80 +/- 0.83 and 5.82 +/- 0.83 mg/L*h) with longer elimination half-life (t(1/2)) (15.43 +/- 2.12 hours vs 2.25 +/- 0.22 and 1.43 +/- 0.18 hours) and mean residence time (7.65 +/- 0.97 hours vs 3.61 +/- 0.41 and 2.34 +/- 0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU.
- 出版日期2016
