冰片修饰金丝桃苷脂质体的制备及经鼻给药药动学行为和脑靶向性考察  

Preparation of borneol modified hyperoside liposomes and investigate of pharmacokinetic behavior and brain-targeting effects through transnasal administration

作　　者：陈晨 王彦阁 宋亚男 丁林 赵新永 决利利 崔锋 CHEN Chen;WANG Yange;SONG Yanan;DING Lin;ZHAO Xinyong;JUE Lili;CUI Feng(Zhengzhou University of Industrial Technology,Zhengzhou 451100,China;Bozhou Hi-tech Innovation Pharmaceutical Industry Technology Research Institute Co.,Ltd.,Bozhou 236839,China)

机构地区：[1]郑州工业应用技术学院,河南郑州451100 [2]亳州高新科创医药产业技术研究院有限公司,安徽亳州236839

出　　处：《中草药》2025年第6期1967-1978,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(23B310010);亳州市重点研发计划(bzzc2021044);河南省医学教育研究项目(WJLX2023148);教育部产学合作协同育人项目(231107272082803)。

摘　　要：目的制备冰片修饰的金丝桃苷脂质体(borneol modified hyperoside liposomes,BM-Hyp-Lips),并进行其脑靶向性考察。方法单因素分别考察处方工艺对BM-Hyp-Lips包封率的影响,选择磷脂与药物用量比、磷脂与胆固醇用量比、药物与冰片用量比作为主要影响因素,采用Box-Behnken设计-响应面法(Box-Behnken design-response surface method,BBD-RSM)优化BM-Hyp-Lips处方。测定包封率、载药量、粒径和ζ电位,透射电子显微镜观察BM-Hyp-Lips形貌,透析袋法考察BMHyp-Lips释药行为。以金丝桃苷原料药iv为参考,考察BM-Hyp-Lips经鼻给药的药动学行为与脑靶向性。结果BM-Hyp-Lips最佳处方为金丝桃苷用量30 mg,磷脂与药物用量比11.3∶1,磷脂与胆固醇用量比6.2∶1,药物与冰片用量比8.7∶1。BMHyp-Lips的平均包封率、载药量、粒径和ζ电位分别为(86.54±0.96)%、(5.89±0.13)%、(208.71±7.83)nm和(−20.94±1.26)mV。BM-Hyp-Lips外貌呈圆形或椭圆形囊泡状,BM-Hyp-Lips释药行为符合Weibull模型,方程为lnln[1/(1-Mt/M∞)]=0.5982 lnt-1.1588。与金丝桃苷原料药经鼻给药相比,BM-Hyp-Lips经鼻给药的相对生物利用度提高至2.39倍,脑组织Cmax和AUC0~t分别提高至3.91倍和5.87倍,脑靶向指数和鼻-脑直接转运率分别提高至313.26%和68.08%。结论BM-Hyp-Lips包封率较高,缓释作用明显,储存稳定性良好,经鼻给药后显著提高了金丝桃苷的生物利用度,并具有较强脑靶向性。Objective To prepare borneol modified hyperoside liposomes(BM-Hyp-Lips),and to investigate its brain-targeting characteristic in vivo.Methods The effects of formulations on the encapsulation rate of BM-Hyp-Lips were investigated by single factor.Phospholipids to drug ratio,phospholipids to cholesterol ratio,and borneol to drug ratio were used as main influencing factors,Box-Behnken design-response surface method(BBD-RSM)was employed to optimize prescriptions of BM-Hyp-Lips.Encapsulation rate,drug loading,particle size andζpotential were determined.The appearance of BM-Hyp-Lips was observed by transmission electron microscopy(TEM),and the drug release behavior was investigated by dialysis bag method.Compared with hyperoside bulk drug injection,the pharmacokinetic behavior and brain-targeting characteristic of BM-Hyp-Lips by transnasal administration were studied.Results Optimal formulation of BM-Hyp-Lips was as follows:hyperoside dose was 30 mg,ratio of phospholipids to drug was 11.3:1,ratio of phospholipids to cholesterol was 6.2:1,and the ratio of drug to borneol was 8.7:1.Encapsulation efficiency,drug loading,particle size andζpotential of BM-Hyp-Lips were(86.54±0.96)%,(5.89±0.13)%,(208.71±7.83)nm and(–20.94±1.26)mV.BM-Hyp-Lips are round or oval vesicles in appearance,release behavior of BM-Hyp-Lips accorded with Weibull model,and the equation was lnln[1/(1-Mt/M∞)]=0.5982 lnt-1.1588.Compared with hyperoside bulk drug,relative bioavailability of BM-Hyp-Lips was increased to 2.39 times,Cmax and AUC0—t of brain tissue of BM-Hyp-Lips were increased to 3.91 and 5.87 times,respectively.What’s more,braintargeting index and nose-to-brain direct transport percentage of BM-Hyp-Lips were increased to 313.26%and 68.08%,respectively.Conclusion BM-Hyp-Lips had high encapsulation rate,obvious sustained-release effect,good storage stability,could significantly improve the bioavailability of hypericin after transnasal administration,and had a good characteristic of brain-targeting.

关 键 词：金丝桃苷 冰片 脂质体 Box-Behnken响应面法 药动学 脑靶向指数 鼻-脑直接转运率 

分 类 号：R283.6[医药卫生—中药学]