莫匹罗星壳聚糖纳米粒原位凝胶的制备与体外抗菌活性研究

目的：制备莫匹罗星壳聚糖纳米粒（Mupirocin-loaded chitosan nanoparticles，Mup-loaded CNs）原位凝胶，并考察其体外抗菌活性。方法：采用离子凝胶化法制备Mup-loaded CNs，以药物与壳聚糖比例（X₁）、pH值（X₂）、搅拌速度（X₃）作为考察对象，以药物包封率（Y）作为评价指标，运用Box-Behnken实验设计法优化Mup-loaded CNs处方和制备工艺；采用Malvern Zetasizer Nano型激光粒度仪测定其粒径分布和Zeta电位，透射电镜观察微观形态；以泊洛沙姆407作为凝胶基质将Mup-loaded CNs制备成原位凝胶；并比较了莫匹罗星软膏、Mup-loaded CNs以及原位凝胶的体外抗菌活性。结果：优化得到Mup-loaded CNs处方组成及制备工艺为：药物与壳聚糖比例为0.2、pH值为3.5、搅拌速度为350 r·min^-1，Mup-loaded CNs的包封率为（89.5±1.8）%，平均粒径为（217.8±10.5） nm，PdI为（0.158±0.015），Zeta电位为（24.8±1.8） mV；在透射电镜下可观察到Mup-loaded CNs呈近似呈球形或类球形分布，粒径分布较均匀；Mup-loaded CNs原位凝胶对金黄色葡萄球菌、大肠杆菌均有较好的抗菌效果。结论：Mup-loaded CNs原位凝胶处方设计合理，制备工艺简单，具有良好的物理性能和抗菌活性，有望成为Mup外用给药的一种新途径。

Preparation and in vitro antibacterial activity of mupirocin-loaded chitosan nanoparticles in situ gels

OBJECTIVE To prepare mupirocin-loaded chitosan nanoparticles (Mupirocin-loaded chitosan nanoparticles,Mup-loaded CNs)in situ gels and investigate their antibacterial activity in vitro.METHODS Mup-loaded CNs were prepared by ionic gelation method.The ratios of drug and chitosan (X₁),pH value (X₂) and stirring speed (X₃) were investigated.The drug encapsulation efficiency (Y) was used as an evaluation index.Malvern Zetasizer Nano laser analyzer was used to determine its particle size distribution and zeta potential.The formulation and preparation process of Mupirocin-loaded CNs were optimized by Box-Behnken experimental design method.The particle size distribution and Zeta potential were determined by Malvern Zetasizer Nano Laser Particle Sizer.Transmission electron microscopy was used to observe the microscopic morphology.Mup-loaded CNs in situ gelswas prepared with poloxamer 407 as gel matrix.And the in vitro antibacterial activity among mupirocin ointment,Mup-loaded CNs and chitosan nanoparticles in situ gels was compared.RESULTS The formulation composition and preparation process of mup-loaded CNs was optimized as follows:the ratio of drug to chitosan was 0.2,pH value was 3.5,stirring speed was 350 r·min^-1,and the encapsulation efficiency of Mup-loaded CNs was (89.5±1.8)%.The average particle size was (217.8±10.5) nm,and the zeta potential was (24.8±1.8) mV.Transmission electron microscopy showed that the Mup-loaded CNs exhibited an approximately spherical distribution with a more uniform particle size distribution.Mup-loaded CNs in situ gels hada good antibacterial effect against Staphylococcus aureus and Escherichia coli.CONCLUSION Mup-loaded CNs insitu gels arewell-designed with simple preparation process,good physical properties and antibacterial activity,and is expected to become a new way for topical administration of mupirocin.