金丝桃苷混合纳米胶束的制备及其肠吸收研究
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篇名: 金丝桃苷混合纳米胶束的制备及其肠吸收研究
TITLE: Study on the preparation of hyperoside mixed nanomicelles and its intestinal absorption
摘要: 目的 制备金丝桃苷混合纳米胶束(Hyp-F127/TPGS)并优化其制备工艺,考察其肠吸收特性。方法采用薄膜分散法制备Hyp-F127/TPGS。在单因素实验和Plackett-Burman实验设计的基础上,结合Box-Behnken响应面法,以包封率和载药量为考察指标,以F127-TPGS质量比、水化时间、Hyp投药量为因素,优化其制备工艺并验证;观察按最优工艺所制Hyp-F127/TPGS的外观、微观形态并测定其粒径、多分散性指数(PDI)和Zeta电位;考察空白胶束(F127/TPGS)的临界胶束浓度(CMC)、Hyp-F127/TPGS的体外释放行为和初步稳定性,利用大鼠在体单向肠灌流模型评价Hyp-F127/TPGS肠吸收特性。结果Hyp-F127/TPGS的最优制备工艺为:F127-TPGS质量比2∶1、水化时间2h、Hyp投药量9mg;3次验证实验结果显示,所制Hyp-F127/TPGS的包封率为(87.20±0.99)%,载药量为(5.02±1.20)%,与预测值的偏差分别为0.92%和2.39%。按最优工艺所制胶束为黄色澄清透明溶液,具有良好的丁达尔效应;透射电子显微镜下呈球形,形态完整且分布均匀,粒径为(15.02±0.16)nm,PDI为0.092±0.031,Zeta电位为(-6.67±1.47)mV;F127/TPGS的CMC为21μg/mL,Hyp-F127/TPGS在4℃下存放4周的稳定性良好;Hyp-F127/TPGS和Hyp对照品的累积释放率分别为(66.30±2.93)%(96h)、(99.24±0.27)%(60h);Hyp-F127/TPGS和Hyp对照品在各肠段均有吸收,主要吸收部位分别为空肠和十二指肠,前者的药物吸收速率常数和表观吸收系数均显著高于后者(P<0.05或P<0.01)。结论优化所得Hyp-F127/TPGS制备工艺稳定、可行;所制Hyp-F127/TPGS具有缓释效果,并在一定程度上促进了Hyp的肠吸收。
ABSTRACT: OBJECTIVE To prepare hyperoside mixed nanomicelles (Hyp-F127/TPGS) and optimize its preparation technology,and to investigate its intestinal absorption characteristics. METHODS Hyp-F127/TPGS was prepared by thin film dispersion method. Based on single factor test and Plackett-Burman design ,combined with Box-Behnken response surface method , the preparation process was optimized and validated using entrapped efficiency (EE)and drug loading (DL)as evaluation indexes , F127-TPGS mass ratio ,hydration time and the amount of Hyp as factors. The appearance and microscopic morphology of Hyp-F127/TPGS obtained by the optimal technology were observed ,and the particle size ,polydispersity index (PDI)and Zeta potential were also determined. The critical micelle concentration (CMC)of blank micelle (F127/TPGS),in vitro release behavior and preliminary stability of Hyp-F 127/TPGS were investigated ,and absorption characteristics of Hyp-F 127/TPGS were investigated by in situ unidirectional intestinal perfusion model. RESULTS The optimal preparation technology of Hyp-F 127/TPGS included F127-TPGS mass ratio of 2∶1,hydration time of 2 h,and Hyp amount of 9 mg. Results of three validation tests showed that the EE of Hyp-F 127/TPGS was (87.20±0.99)%,and the DL was (5.02±1.20)%,deviations from predicted values were 0.92% and 2.39%. The micelles prepared by optimal technology were yellow ,clear and transparent solution ,with good Tyndall effect ;under transmission electron microscope ,they were spherical ,complete and evenly distributed ;the particle size was (15.02±0.16)nm, the PDI was 0.092±0.031,and the Zeta potential was (-6.67±1.47)mV. The CMC of F 127/TPGS was 21 μg/mL,Hyp-F127/ TPGS was stable after 4 weeks of storage at 4 ℃,and the cumulative release rates of Hyp-F 127/TPGS and Hyp control were (66.30±2.93)%(96 h)and(99.24±0.27)%(60 h),respectively. Hyp-F 127/TPGS and Hyp reference were absorbed in each intestinal segment ,and the main absorption sites were jejunum and duodenum respectively ;drug absorption rate constant andapparent absorption coefficient of the former were significantly higher than those of the latter (P<0.05 or P<0.01). E-mail:zhangyuhangxz@163.com CONCLUSIONS The optimized preparation technology of Hyp-F127/TPGS is stable and feasible ;prepared Hyp-F 127/ TPGS shows a sustained -release effect ,which promotes the intestinal absorption of H yp to a certain extent.
期刊: 2022年第33卷第10期
作者: 张宇航,邱智东,邱野,王伟楠,刁元元,石羽文,姜孟成,刘伟朋,贾艾玲
AUTHORS: ZHANG Yuhang,QIU Zhidong, QIU Ye,WANG Weinan,DIAO Yuanyuan,SHI Yuwen,JIANG Mengcheng,LIU Weipeng,JIA Ailing
关键字: 金丝桃苷;混合纳米胶束;制备工艺;肠吸收特性;Plackett-Burman设计;Box-Behnken响应面法;单向肠灌流模型
KEYWORDS: hyperoside;mixed nanomicelles ;preparation technology ;intestinal absorption characteristics ;Plackett-Burman
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