目的 制備包載金絲桃苷的磷脂酰膽堿/殼聚糖自組裝納米粒（hyperoside self-assembled phosphatidylcholine chitosan nanoparticles，Hyp-PC/CS-NPs），并考察相對口服吸收生物利用度。方法 單因素考察Hyp-PC/CS-NPs制備的主要影響因素，使用Box-Behnken設(shè)計-效應(yīng)面法篩選Hyp-PC/CS-NPs處方。透射電子顯微鏡（transmission electron microscope，TEM）觀察Hyp-PC/CS-NPs形貌；制備Hyp-PC/CS-NPs凍干粉并測定其飽和溶解度；傅里葉變換紅外光譜（Fourier transform infrared spectroscopy，F(xiàn)TIR）研究Hyp-PC/CS-NPs凍干粉及各組分的結(jié)合機制；X射線粉末衍射法（X-ray powder diffraction，XRPD）分析金絲桃苷晶型；考察Hyp-PC/CS-NPs凍干粉及金絲桃苷原料藥的體外釋藥行為；測定Hyp-PC/CS-NPs凍干粉的沉降率并考察其儲存穩(wěn)定性。SD大鼠分別ig給予金絲桃苷原料藥和Hyp-PC/CS-NPs凍干粉，考察其口服藥動學(xué)行為，并計算Hyp-PC/CS-NPs相對口服生物利用度。結(jié)果 Hyp-PC/CS-NPs最佳處方：藥物質(zhì)量濃度為0.37 mg/mL，磷脂酰膽堿與殼聚糖質(zhì)量比為16.3∶1，磷脂酰膽堿與金絲桃苷質(zhì)量比為7.9∶1。Hyp-PC/CS-NPs的包封率、載藥量、粒徑及ζ電位分別為（84.19±1.23）%、（8.81±0.16）%、（166.18±4.03）nm和（32.39±0.95）mV；Hyp-PC/CS-NPs外貌為類球形，金絲桃苷可能與載體發(fā)生了氫鍵絡(luò)合作用；金絲桃苷以無定型形態(tài)存在于Hyp-PC/CS-NPs凍干粉中；與原料藥相比，Hyp-PC/CS-NPs凍干粉中的金絲桃苷在模擬胃液、蒸餾水和模擬腸液中的飽和溶解度分別增加了7.22、4.04、5.10倍。藥動學(xué)結(jié)果顯示，與金絲桃苷原料藥或物理混合物相比，Hyp-PC/CS-NPs藥動學(xué)參數(shù)均極顯著性增加（P＜0.01）；Hyp-PC/CS-NPs中金絲桃苷相對口服生物利用度增加至其原料藥的4.11倍。結(jié)論 成功制備了Hyp-PC/CS-NPs及其凍干粉，Hyp-PC/CS-NPs明顯改變了金絲桃苷的體內(nèi)藥動學(xué)行為，顯著增加了其口服生物利用度，為其后續(xù)藥效學(xué)評價奠定實驗基礎(chǔ)。

Objective To prepare hyperoside self-assembled phosphatidylcholine chitosan nanoparticles (Hyp-PC/CS-NPs), and relative oral bioavailability were studied. Methods The main influencing factors of Hyp-PC/CS-NPs were investigated by single factor experiments, Box-Behnken design-response surface method was employed to optimize prescriptions of Hyp-PC/CS-NPs. Transmission electron microscope (TEM) was employed to observe microscopic appearance of Hyp-PC/CS-NPs, lyophilized powder of Hyp-PC/CS-NPs was prepared and its saturated solubility was determined, Fourier transform infrared spectroscopy (FTIR) was used to investigate the binding mechanism of Hyp-PC/CS-NPs lyophilized powder and each component, and crystal form of hyperoside was analyzed by X-ray powder diffraction (XRPD). Drug release behavior in vitro of Hyp-PC/CS-NPs lyophilized powder and hyperoside was determined, the sedimentation rate of Hyp-PC/CS-NPs lyophilized powder was determined and its storage stability was also investigated. SD rats were administered intragastrically with hyperoside and Hyp-PC/CS-NPs lyophilized powder, its oral pharmacokinetic behavior was studied, and relative oral bioavailability of Hyp-PC/CS-NPs was calculated. Results Optimal formulations of Hyp-PC/CS-NPs: hyperoside concentration was 0.37 mg/mL, phosphatidylcholine to chitosan ratio was 16.3:1, phosphatidylcholine to hyperoside ratio was 7.9:1. Envelopment efficiency, drug loading, particle size and ζ potential were (84.19 ±1.23)%, (8.81 ±0.16)%, (166.18 ±4.03) nm and (32.39 ±0.95) mV, respectively. Appearance of Hyp-PC/CS-NPs was spherical, hyperoside may have complexed with the carrier by hydrogen bond. The state of hyperoside changed into an amorphous form in Hyp-PC/CS-NPs freeze-dried powder. Solubility of hyperoside in simulated gastric juice, distilled water and simulated intestinal juice was increased by 7.22, 4.04 and 5.10 times, respectively. Pharmacokinetic results showed that the pharmacokinetic parameters of Hyp-PC/CS-NPs were significantly increased compared with hyperoside or physical mixture (P < 0.01), and the relative bioavailability of hyperoside in Hyp-PC/CS-NPs was increased to 4.11 times. Conclusion Hyp-PC/CS-NPs and its lyophilized powder were successfully prepared, pharmacokinetic behavior of hyperoside in vivo was greatly changed, and bioavailability of hyperoside was significantly increased by Hyp-PC/CS-NPs, which established the experimental foundation for the follow-up pharmacodynamic evaluation.

R283.6

河南省高等學(xué)校重點科研項目計劃（23B310010）;河南省醫(yī)學(xué)教育研究項目（WJLX2023153）;黑龍江省重點研發(fā)計劃（GA22C004）