载三氧化二砷壳聚糖微球的制备、表征及释药性能

目的:探讨载三氧化二砷(arsenic trioxide,As2O3)壳聚糖微球的制备工艺,并观察其表征和体外药物释放效果。方法:以三聚磷酸钠混合丙酮为凝胶浴,采用静电液滴法制备载As2O3壳聚糖微球。光镜和电镜下观察所得载药微球的成球效果,并进行粒径分析、红外光谱(Fourier transform infrared,FT-IR)和X-射线衍射分析。另将载As2O3壳聚糖微球置于模拟体液中,定时提取样本液,采用原子荧光法检测砷的释放量,从而评价载药微球的药物释放效果。结果:载As2O3壳聚糖微球外观圆整、均匀度好、颗粒形状规则无粘连,具有良好的分散性。这种载药微球的粒径为(239.5±11.2)μm,包封率为(87.3±6.5)%。FT-IR和X-射线衍射分析都表明三聚磷酸钠在微球制备中起到了较好的离子交联作用,能降低壳聚糖的结晶度,提高其水溶性。在最初4 h内载药微球的药物释放迅速,之后则平缓上升,24 h内药物释放量仅为(30.8±0.5)%。结论:采用静电液滴法制备载As2O3壳聚糖微球,工艺简单可靠,所得载药微球水溶性较好,表征较为满意,包封率高,药物释放较为平缓,在载药骨修复材料的研究中具有潜在的优势。

Preparation,Characterization and Drug Release Property of Chitosan Microspheres Loaded with Arsenic Trioxide

Objective：To study the technique for preparing chitosan microspheres loaded with arsenic trioxide（As2O3 ） ,and its characterization and drug release property in vitro. Methods：Chitosan microspheres loaded with As2O3 were prepared through the electrostatic droplet generation technique using the mixture of sodium tripolyphosphate and acetone as coagulation bath. Drug-loaded chitosan microspheres were observed by optical microscope and scanning electron microscope. Particle diameter, Fourier transform infrared（FT-IR） spectra and X-ray diffraction result were analyzed. Then the microspheres were were placed in simulated body fluid. The arsenic dose of sample extracted at different time was detected by atomic fluorescence spectrometry so as to estimate drug release property. Results： The drug-loaded chitosan microspheres looked round and regular without adhe- sion between them,and had good uniformity and dispersion. The mean particle diameter was （239.5 ±11.2）/2m and encapsula- tion efficiency was （87.3 ± 6.5） %. FT-IR and X-ray diffraction analysis showed that sodium tripoiyphosphate had a good effect on ionic crosslinking during microspheres formation. As reducing crystallinity of chitosan, sodium tripolyphosphate could also increase microspheres＇ water solubility. Release of As2O3 was rapid up to 4 h followed by a slow release status. Percentage of drug release was up to only （30.8 ＋ 0.5）% in 24 h. Conclusions： The electrostatic droplet generation technique for preparing chitosan microspheres loaded with As2O3 is simple and feasible. The resulting microspheres has good water solubility, satisfied characterization,high encapsulation efficiency and gentle drug release, which has potential advantages during the research of drug-loaded bone repair material consequently.