聚羟基丁酸与羟基辛酸-阿奇霉素缓释微球的研究  

Study on azithromycin-loaded poly(3-hydroxybutyarte-co-3-hydroxyoctanoate)microspheres

作　　者：张婵[1] 陈璋[1] 张晓艳[1] 林汲[1] 赵良启[1] 董岳峰 

机构地区：[1]山西大学生物技术研究所,030006 [2]山西省医药与生命科学研究院

出　　处：《山西医药杂志（上半月）》2010年第8期690-693,共4页Shanxi Medical Journal

基　　金：国家自然科学基金(50573045)

摘　　要：目的研究聚羟基丁酸与羟基辛酸(PHBHOx)载阿奇霉素微球的制备技术、体外性能及在小鼠体内的药代动力学行为。方法采用静电纺丝法制备PHBHOx载阿奇霉素微球,运用三因素三水平响应面法优化了制备工艺条件。以pH7.4磷酸盐缓冲液(PBS)为释放介质考察了微球的体外释药性能。通过尾静脉将微球注入小鼠体内,运用高效液相色谱法(HPLC)检测了药代动力学参数。结果微球制备的最适条件为:PH-BHOx的浓度为6.47%,阿奇霉素与PHBHOx质量比为1∶2.7,静电电压为12kV。在扫描电镜下,微球呈圆球形,外观较圆整;粒径分布均匀,在3～30μm;包封率达60%以上;体外释放45d累计释药率达80%,释药曲线符合Higuchi方程。与阿奇霉素溶液相比,小鼠尾静脉注射PHBHOx载阿奇霉素微球后,药物的达峰浓度显著降低,具有较好的缓释性能。结论 PHBHOx载阿奇霉素微球的制备技术可行,重现性好,有望构建一个新的长效缓释给药系统,并为进一步开展靶向PHBHOx载药缓释微球制剂的研究奠定了基础。Objective The aim of this paper is to prepare and optimize azithromycin（AZI）-loaded poly（3-hydroxybutyrate-co-3-hydroxyoctanoate）[PHBHOx] microspheres and to investigate its pharmacokinetics in mice.Methods Microspheres were prepared by electrospinning technique and optimized using response surface methodology.The characteristics of in vitro drug release in pH7.4 phosphate buffer（PBS）and the behaviors of pharmacokinetics in mice were examined and evaluated by high performance liquid chromatography（HPLC）.Results The optimal conditions of preparing microspheres were as follows：the voltage was 12 kV,the ratio of AZI and PHBHOx was 1∶2.7,and the concentration of PHBHOx was 6.47%（W/V）.The AZI-loaded microspheres were spherical and smooth,and the sizes of microspheres showed a narrow monodisperse size distribution approximately from 3 to 30 μm.The encapsulation efficiency was above 60%.The accumulative release in vitro was 80% for 45 days and was well described by Higuchi＇ equation.The pharmacokinetics following iv administration of the microspheres in mice showed that the peak concentration of AZI was lower.Conclusion The prepare method of AZI-loaded PHBHOx is available and good reproducibility,and may be helpful to construct a long-effect sustained release drug delivery system and establish the foundation for the study on targeting sustained drug release-loaded PHBHOx microsphere.

关 键 词：聚羟基丁酸与羟基辛酸 阿奇霉素 微球体 响应面法 

分 类 号：R944[医药卫生—药剂学]