目的 制备橘红素纳米结构脂质载体（tangeretin nanostructured lipid carriers，Tan-NLCs）和橘红素固体脂质纳米粒（tangeretin solid lipid nanoparticles，Tan-SLNs），考察相对口服吸收生物利用度。方法 采用包封率、载药量和粒径为指标，单因素结合Box-Behnken设计-效应面法（Box-Behnken design-response surface methodology，BBD-RSM）优化Tan-NLCs处方，并制备Tan-SLNs。透射电子显微镜观察Tan-NLCs和Tan-SLNs外貌形态，考察在pH 2.0和pH 6.8磷酸盐缓冲液（PBS）中的释药情况。X射线粉末衍射（X-ray powder diffraction，XRPD）法和示差量热扫描（differential scanning calorimetry，DSC）法对晶型进行分析，并考察Tan-NLCs和Tan-SLNs冻干粉的稳定性。以橘红素原料药为参考，比较Tan-NLCs和Tan-SLNs口服药动学行为。结果 Tan-NLCs和Tan-SLNs平均包封率分别为（85.13±1.01）%和（73.07±1.38）%，载药量分别为（5.43±0.19）%和（4.11±0.22）%，粒径分别为（184.77±8.63）nm和（226.09±10.25）nm。Tan-NLCs和Tan-SLNs呈椭圆形或球形，橘红素在Tan-NLCs和Tan-SLNs冻干粉中可能以无定型形式存在，其释药速率和累积释放率明显提高。Tan-NLCs冻干粉稳定性高于Tan-SLNs冻干粉。口服药动学结果显示，Tan-SLNs冻干粉C_max和相对口服吸收生物利用度分别提高至2.01倍和3.10倍；Tan-NLCs冻干粉C_max和相对口服吸收生物利用度分别提高至2.83倍和4.59倍。结论 Tan-NLCs和Tan-SLNs均可促进橘红素口服吸收，但Tan-NLCs冻干粉稳定性更高，促吸收作用更大。

Objective To prepare tangeretin nanostructured lipid carriers (Tan-NLCs) and tangeretin solid lipid nanoparticles (Tan-SLNs), and investigate the oral relative bioavailability. Methods Encapsulation efficiency, drug loading and particle size were employed as indexes, single factor experiments combined with Box-Behnken design-response surface method (BBD-RSM) was used to gain optimal prescriptions of Tan-NLCs, and Tan-SLNs were also prepared. Morphology of Tan-NLCs and Tan-SLNs were observed by transmission electron microscopy (TEM), and the drug release was investigated in pH 2.0 and pH 6.8 phosphate buffer (PBS). Crystal forms were studied by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). The stability of Tan-NLCs and Tan-SLNs lyophilized powders were investigated. Using tangeretin as a control, oral pharmacokinetics behavior of Tan-NLCs and Tan-SLNs in vivo was compared. Results Encapsulation efficiencies of Tan-NLCs and Tan-SLNs were (85.13 ±1.01)% and (73.07 ±1.38)%, drug loading efficiencies were (5.43 ±0.19)% and (4.11 ±0.22)%, particle sizes were (184.77 ±8.63) nm and (226.09 ±10.25) nm, respectively. Tan-NLCs and Tan-SLNs are elliptical or spherical. The state of tangeretin might change into an amorphous state in Tan-NLCs and Tan-SLNs lyophilized powders, release rate and cumulative release rate of tangeretin were obviously increased. The stability of Tan-NLCs lyophilized powder was higher than that of Tan-SLNs lyophilized powder. Results of oral pharmacokinetics showed that C_max and relative oral bioavailability of Tan-SLNs lyophilized powder were increased to 2.01 and 3.10 times, respectively. C_max and relative oral bioavailability of Tan-NLCs lyophilized powder were increased to 2.83 and 4.59 times, respectively. Conclusion Tan-NLCs and Tan-SLNs can promote oral absorption of tangeretin, but Tan-NLCs lyophilized powder has higher stability and greater absorption.

R283.6

河南省高等学校重点科研项目计划（23B320013）；河南应用技术职业学院骨干教师（2020-GGJS-Y008）；妇科肿瘤科研创新团队（2021-TD-02）；河南应用技术职业学院2023年度校级课题（2023-K.J-54）