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BM-Hyp-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。BM-Hyp-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－M_t/M_∞)]＝0.598 2 lnt－1.158 8。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C_max和AUC_0～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 and ζ potential 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 and ζ potential 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－M_t/M_∞)] = 0.598 2 lnt－1.158 8. Compared with hyperoside bulk drug, relative bioavailability of BM-Hyp-Lips was increased to 2.39 times, C_max and AUC_0—t of brain tissue of BM-Hyp-Lips were increased to 3.91 and 5.87 times, respectively. What’s more, brain-targeting 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.

R283.6

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）