栀子苷经鼻给药醇质体喷雾剂的制备及其体外鼻黏膜渗透性研究  

Preparation of nasal ethosome spray of geniposide and its nasal mucosa permeability in vitro

作　　者：宋艳丽[1] 韩腾飞[1] 李莎莎[1] 危红华[1] 吴艳丽[1] 张朵朵[1] 郝保华[1] 

机构地区：[1]西北大学生命科学学院中药系,陕西西安710069

出　　处：《中草药》2013年第9期1105-1110,共6页Chinese Traditional and Herbal Drugs

基　　金：国家重大新药创制科技重大专项(2009ZX09502-019);陕西省教育厅产业培育项目(2010JC20)

摘　　要：目的研究栀子苷经鼻给药醇质体喷雾剂的最佳制备工艺,并考察其体外鼻黏膜渗透性规律和该制剂的鼻黏膜纤毛毒性。方法采用注入法制备栀子苷醇质体,以包封率为评价指标,应用星点设计-效应面法对栀子苷醇质体制备过程中有关影响因素及工艺参数进行优化;采用透射电镜和光子相关光谱仪考察其药剂学性质;以离体猪鼻腔黏膜为模型,考察栀子苷醇质体喷雾剂的体外透黏膜给药规律,并与其脂质体及水溶液进行比较;以在体蟾蜍口腔上腭纤毛在药物溶液作用下持续摆动的时间评价制剂的鼻黏膜纤毛毒性。结果最优处方条件下制备的栀子苷醇质体粒径为(173.40±71.02)nm,Zeta电位为(42.50±8.27)mV,包封率为(65.80±2.53)%,载药量为(5.25±0.15)%。栀子苷醇质体300 min经鼻黏膜单位面积渗透量为23.39μg/cm2,是其脂质体的2.17倍、水溶液的11.03倍。此外,该制剂基本无鼻黏膜纤毛毒性。结论优选得到的栀子苷醇质体处方和制备工艺合理,能够显著提高栀子苷的鼻黏膜渗透性,可用于鼻腔给药。Abstract： Objective To optimize the preparation technology of geniposide ethosome Spray （GES） and to evaluate the regulation of its nasal mucosa permeability in vitro and nasal ciliotoxicity. Methods Geniposide ethosomes were prepared by ethanol injection method. An central composite design-response surface method was used to optimize the related factors and technical parameters in the preparation of geniposide ethosomes with entrapment efficiency as evaluation index. Their physical properties were evaluated by the transmission electron microscope and photon correlation spectrometer. The isolated pig nasal mucosa was used to investigate the regulation of GES nasal mucosa permeability in vitro. The accumulated permeation amounts of geniposide aqueous solution, geniposide liposomes, and geniposide ethosomes were compared. In situ toad palate model was established to evaluate the effects of geniposide ethosomes on persistent vibration duration of toad palate cilia, so as to evaluate the cililary toxicity. Results The average encapsulation percentage, particle size, drug loading, and Zeta potential of geniposide ethosomes were （65.80 ± 2.53）%, （173.40 ± 71.02） nm, （5.25 ±0.15）%, and （-42.50 ±8.27） mV, respectively. The accumulative permeation amount of geniposide ethosomes in 300 min was 23.39 pg/cm^2, which was about 2.17 times of liposomes and 11.03 times of geniposide aqueous solution. Furthermore, the GES showed less mucociliary toxicity. Conclusion The optimized formulation and preparation technology of geniposide ethosomes are rational. GES could significantly increase the mucosa permeability of geniposide and could be used for nasal administration.

关 键 词：栀子苷 醇质体喷雾剂 星点设计-效应面法 鼻腔给药 纤毛毒性 

分 类 号：R283.6[医药卫生—中药学]