目的 制備冰片修飾的金絲桃苷脂質(zhì)體（borneol modified hyperoside liposomes，BM-Hyp-Lips），并進(jìn)行其腦靶向性考察。方法 單因素分別考察處方工藝對BM-Hyp-Lips包封率的影響，選擇磷脂與藥物用量比、磷脂與膽固醇用量比、藥物與冰片用量比作為主要影響因素，采用Box-Behnken設(shè)計-響應(yīng)面法（Box-Behnken design-response surface method，BBD-RSM）優(yōu)化BM-Hyp-Lips處方。測定包封率、載藥量、粒徑和ζ電位，透射電子顯微鏡觀察BM-Hyp-Lips形貌，透析袋法考察BM-Hyp-Lips釋藥行為。以金絲桃苷原料藥iv為參考，考察BM-Hyp-Lips經(jīng)鼻給藥的藥動學(xué)行為與腦靶向性。結(jié)果BM-Hyp-Lips最佳處方為金絲桃苷用量30 mg，磷脂與藥物用量比11.3∶1，磷脂與膽固醇用量比6.2∶1，藥物與冰片用量比8.7∶1。BM-Hyp-Lips的平均包封率、載藥量、粒徑和ζ電位分別為（86.54±0.96）%、（5.89±0.13）%、（208.71±7.83）nm和（−20.94±1.26）mV。BM-Hyp-Lips外貌呈圓形或橢圓形囊泡狀，BM-Hyp-Lips釋藥行為符合Weibull模型，方程為lnln[1/(1－M_t/M_∞)]＝0.598 2 lnt－1.158 8。與金絲桃苷原料藥經(jīng)鼻給藥相比，BM-Hyp-Lips經(jīng)鼻給藥的相對生物利用度提高至2.39倍，腦組織C_max和AUC_0～t分別提高至3.91倍和5.87倍，腦靶向指數(shù)和鼻-腦直接轉(zhuǎn)運(yùn)率分別提高至313.26%和68.08%。結(jié)論BM-Hyp-Lips包封率較高，緩釋作用明顯，儲存穩(wěn)定性良好，經(jīng)鼻給藥后顯著提高了金絲桃苷的生物利用度，并具有較強(qiáng)腦靶向性。

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

河南省高等學(xué)校重點(diǎn)科研項(xiàng)目計劃（23B310010）；亳州市重點(diǎn)研發(fā)計劃（bzzc2021044）；河南省醫(yī)學(xué)教育研究項(xiàng)目（WJLX2023148）；教育部產(chǎn)學(xué)合作協(xié)同育人項(xiàng)目（231107272082803）