橘红素2种脂质纳米粒的制备、表征和口服吸收生物利用度评价  

Two kinds of tangeretin lipid-based nanoparticles: Preparation, characterization and oral bioavailability evaluation

作　　者：李伟宏 高娟 王风云 郑岩 LI Wei-hong;GAO Juan;WANG Feng-yun;ZHENG Yan(Henan Vocational College of Applied Technology,Zhengzhou 450042,China;Shanghai Institute of Pharmaceutical Industry,Shanghai 201203,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042 [2]上海医药工业研究院,上海201203

出　　处：《中草药》2023年第24期8031-8042,共12页Chinese Traditional and Herbal Drugs

基　　金：河南省高等学校重点科研项目计划(23B320013);河南应用技术职业学院骨干教师(2020-GGJS-Y008);妇科肿瘤科研创新团队(2021-TD-02);河南应用技术职业学院2023年度校级课题(2023-K.J-54)。

摘　　要：目的 制备橘红素纳米结构脂质载体(tangeretin nanostructured lipid carriers,Tan-NLCs)和橘红素固体脂质纳米粒(tangeretin solid lipid nanoparticles,Tan-SLNs),考察相对口服吸收生物利用度。方法 采用包封率、载药量和粒径为指标,单因素结合Box-Behnken设计-效应面法(Box-Behnken design-response surface methodology,BBD-RSM)优化Tan-NLCs处方,并制备Tan-SLNs。透射电子显微镜观察Tan-NLCs和Tan-SLNs外貌形态,考察在pH 2.0和pH 6.8磷酸盐缓冲液(PBS)中的释药情况。X射线粉末衍射(X-ray powder diffraction,XRPD)法和示差量热扫描(differential scanning calorimetry,DSC)法对晶型进行分析,并考察Tan-NLCs和Tan-SLNs冻干粉的稳定性。以橘红素原料药为参考,比较Tan-NLCs和Tan-SLNs口服药动学行为。结果 Tan-NLCs和Tan-SLNs平均包封率分别为(85.13±1.01)%和(73.07±1.38)%,载药量分别为(5.43±0.19)%和(4.11±0.22)%,粒径分别为(184.77±8.63)nm和(226.09±10.25)nm。Tan-NLCs和Tan-SLNs呈椭圆形或球形,橘红素在Tan-NLCs和Tan-SLNs冻干粉中可能以无定型形式存在,其释药速率和累积释放率明显提高。Tan-NLCs冻干粉稳定性高于Tan-SLNs冻干粉。口服药动学结果显示,Tan-SLNs冻干粉C_(max)和相对口服吸收生物利用度分别提高至2.01倍和3.10倍;Tan-NLCs冻干粉C_(max)和相对口服吸收生物利用度分别提高至2.83倍和4.59倍。结论 Tan-NLCs和Tan-SLNs均可促进橘红素口服吸收,但Tan-NLCs冻干粉稳定性更高,促吸收作用更大。Objective To prepare tangeretin nanostructured lipid carriers(Tan-NLCs)and tangeretin solid lipid nanoparticles(TanSLNs),and investigate the oral relative bioavailability.Methods Encapsulation efficiency,drug loading and particle size were employed as indexes,single factor experiments combined with Box-Behnken design-response surface method(BBD-RSM)was used to gain optimal prescriptions of Tan-NLCs,and Tan-SLNs were also prepared.Morphology of Tan-NLCs and Tan-SLNs were observed by transmission electron microscopy(TEM),and the drug release was investigated in pH 2.0 and pH 6.8 phosphate buffer(PBS).Crystal forms were studied by X-ray powder diffraction(XRPD)and differential scanning calorimetry(DSC).The stability of TanNLCs and Tan-SLNs lyophilized powders were investigated.Using tangeretin as a control,oral pharmacokinetics behavior of TanNLCs and Tan-SLNs in vivo was compared.Results Encapsulation efficiencies of Tan-NLCs and Tan-SLNs were(85.13±1.01)%and(73.07±1.38)%,drug loading efficiencies were(5.43±0.19)%and(4.11±0.22)%,particle sizes were(184.77±8.63)nm and(226.09±10.25)nm,respectively.Tan-NLCs and Tan-SLNs are elliptical or spherical.The state of tangeretin might change into an amorphous state in Tan-NLCs and Tan-SLNs lyophilized powders,release rate and cumulative release rate of tangeretin were obviously increased.The stability of Tan-NLCs lyophilized powder was higher than that of Tan-SLNs lyophilized powder.Results of oral pharmacokinetics showed that Cmax and relative oral bioavailability of Tan-SLNs lyophilized powder were increased to 2.01 and 3.10 times,respectively.Cmax and relative oral bioavailability of Tan-NLCs lyophilized powder were increased to 2.83 and 4.59 times,respectively.Conclusion Tan-NLCs and Tan-SLNs can promote oral absorption of tangeretin,but Tan-NLCs lyophilized powder has higher stability and greater absorption.

关 键 词：橘红素 纳米结构脂质载体 固体脂质纳米粒 Box-Behnken设计-效应面法 药物释放 药动学 口服生物利用度 

分 类 号：R283.6[医药卫生—中药学]