蒙花苷巯基化纳米胶束的制备、表征及其口服吸收生物利用度评价  

Buddleoside sulfhydryl-modified nanomicelles:Preparation,characterization and oral bioavailability evaluation

作　　者：董亚楠 任书强 柳超 李伟宏 董姣姣 王风云 DONG Ya-nan;REN Shu-qiang;LIU Chao;LI Wei-hong;DONG Jiao-jiao;WANG Feng-yun(Zhengzhou University of Industrial Technology,Zhengzhou 450042,China;Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Peking University Cancer Hospital,Beijing 100142,China)

机构地区：[1]河南应用技术职业学院,河南郑州450042 [2]郑州澍青医学高等专科学校,河南郑州450064 [3]北京大学肿瘤医院,北京100142

出　　处：《中草药》2023年第23期7776-7787,共12页Chinese Traditional and Herbal Drugs

基　　金：2023年度河南省高等学校重点科研项目(23B320013);河南应用技术职业学院青年骨干教师资助项目(2020-GGJS-Y003)。

摘　　要：目的 制备蒙花苷巯基化纳米胶束(buddleoside sulfhydryl-modified nanomicelles,Bud-SH-NMs),考察口服药动学行为。方法 薄膜分散-超声法制备Bud-SH-NMs,单因素实验结合Box-Behnken设计-效应面法(Box-Behnken design-response surface methodology,BBD-RSM)优化处方。X射线粉末衍射法(XRPD)分析晶型,透射电子显微镜(TEM)观察Bud-SHNMs外貌形态,透析法考察在pH 2.0和pH 6.8磷酸盐缓冲液(PBS)中的释药行为。SD大鼠分别ig给予蒙花苷混悬液和Bud-SH-NMs冻干粉,HPLC法测定血药浓度,计算主要药动学参数。结果 Bud-SH-NMs最佳处方:巯基修饰二硬脂酰基磷脂酰乙醇胺-聚乙二醇2000(DSPE-PEG2000-SH)与药物用量比为7.5∶1,水合体积为9.7 mL,水合温度45℃。Bud-SHNMs的包封率、载药量、沉降率、粒径和ζ电位分别为(90.86±1.78)%、(10.76±0.24)%、(4.14±0.29)%、(49.27±6.82)nm和(-18.53±1.12)m V。蒙花苷在Bud-SH-NMs冻干粉中以无定型形式存在,微观外貌为球形,在pH 2.0和pH 6.8 PBS中缓释特征明显,释药过程符合Weibull模型。药动学结果显示,Bud-SH-NMs半衰期(t_(1/2))增加至(5.93±0.96)h,血药浓度(C_(max))和相对口服吸收生物利用度分别提高至2.83倍和5.10倍。结论 Bud-SH-NMs粒径小,包封率高,稳定性好,显著促进了蒙花苷口服吸收,为后续研究奠定基础。Objective To prepare buddleoside sulfhydryl-modified nanomicelles(Bud-SH-NMs)and investigate their oral pharmacokinetic behavior in vivo.Methods Bud-SH-NMs were prepared by thin film dispersion-ultrasonic method.Single factor experiments combined with Box-Behnken response surface design method was used to optimize the prescriptions.Crystal form of Bud-SH-NMs lyophilized powder was analyzed by X-ray powder diffraction(XRPD),and the appearance was observed using transmission electron microscope(TEM).The release behavior of Bud-SH-NMs in pH 2.0 and pH 6.8 phosphate buffers were investigated by dialysis method.SD rats in each group were administered intragastrically with buddleoside suspension and Bud-SHNMs lyophilized powder,respectively.The concentration of buddleoside in plasma was analyzed by HPLC,and main pharmacokinetic parameters were calculated.Results The optimal formulation of Bud-SH-NMs was as follows:DSPE-PEG2000-SH to drug ratio of 7.5:1,hydration volume of 9.7 mL,and hydration temperature of 45℃.Envelopment efficiency,drug loading,settlement rate,particle size andζpotential were(90.86±1.78)%,(10.76±0.24)%,(4.14±0.29)%,(49.27±6.82)nm and(−18.53±1.12)mV,respectively.Buddleoside existed in an amorphous form in Bud-SH-NMs lyophilized powder,and its microscopic appearance was spherical.Sustained release characteristics of Bud-SH-NMs were obvious in pH 2.0 and pH 6.8 phosphate buffer,and drug release process conformed to Weibull model.Pharmacokinetic results showed that t_(1/2) of Bud-SH-NMs was increased to(5.93±0.96)h,C_(max) and oral relative bioavailability was increased to 2.83-fold and 5.10-fold,respectively..Conclusion Bud-SH-NMs had small particle size,high entrapment efficiency and good stability,and promoted oral absorption of buddleoside effectively,which laid the foundation for the following research.

关 键 词：蒙花苷 巯基修饰 纳米胶束 薄膜分散-超声法 Box-Behnken设计-效应面法 药动学 生物利用度 

分 类 号：R283.6[医药卫生—中药学]