载夫西地酸钠壳聚糖纳米粒的制备与体外抑菌活性

Preparation and in vitro antibacterial efficiency of fusidate sodium-loaded chitosan nanoparticles

目的制备夫西地酸钠载药壳聚糖纳米粒(Fus-loaded CNs),并评价其体外抗菌活性。方法以壳聚糖用量(X1)、三聚磷酸钠用量(X2)、探头超声时间(X3)作为考察因素,以纳米粒粒径分布(Y1)和药物包封率(Y2)作为评价指标,通过Box-Behnken响应面法优化得到Fus-loaded CNs最优处方和工艺参数,并考察了Fus-loaded CNs的理化性质以及体外药物释放情况。通过抑菌圈实验比较了Fus原料药与Fus-loaded CNs对金黄色葡萄球菌的体外抗菌活性。结果经实验优化得到Fus-loaded CNs的最优处方和工艺参数为:壳聚糖用量为90 mg,三聚磷酸钠(sodium tripolyphosphate,TPP)用量为33 mg,探头超声时间为3 min,制备的Fus-loaded CNs在透射电镜下可观察到外观圆整,分布均匀,粒径大小为(161.4±9.3)nm,Zeta电位为(14.2±0.9)mV,Fus-loaded CNs体外释放速率表现为先快后慢趋势;Fus-loaded CNs对金黄色葡萄球菌的体外抑菌活性要高于Fus原料药。结论将夫西地酸钠制备成壳聚糖纳米粒,不仅可以降低药物释放速率,减少用药次数,而且提高了药物的抗菌活性,有望成为夫西地酸钠的新型给药形式用于临床治疗。

Objective To prepare fusidate sodium-loaded chitosan nanoparticles(Fus-loaded CNs)and evaluate their in vitro antibacterial efficiencies.Methods In this study,the nanoparticles were prepared using the ionic gelation technique.The amount of chitosan(X1),the amount of sodium tripolyphosphate(X2),and the ultrasonic time(X3)were used as the factors.And the factors impacting the particle size(Y1)and entrapment efficiency(Y2)of the nanoparticles were evaluated using Box-Behnken response surface methodology.The optimized Fus-loaded CNs were characterized and in vitro drug release was evaluated.The in vitro antibacterial efficiency of Fus and Fus-loaded CNs against Staphylococcus aureus was compared by inhibition zone experiments.Results The optimal formulation and process parameters of Fus-loaded CNs were optimized by experiment:the amount of chitosan was 90 mg,the amount of sodium tripolyphosphate was 33 mg,and the ultrasonic time was 3 min.The prepared Fus-loaded CNs could be observed to have a rounded appearance and uniform distribution under the transmission electron microscope.The particle size was(161.4±9.3)and the Zeta potential was(14.2±0.9)mV.The in vitro release rate of Fus-loaded CNs was fast in the first 6 h,followed by the slow release.Fus-loaded CNs had higher in vitro antibacterial efficiency against Staphylococcus aureus than Fus.Conclusion The fusidate sodium-loaded chitosan nanoparticles can reduce the drug release rate and improve the antibacterial efficiency.It is expected to be a new drug delivery form of fusidate sodium for clinical treatment.