目的 优化叶黄素酯（LE）纳米粒（NPs）的制备工艺，并对其水溶性的改善程度进行测试。方法 以四氢呋喃为溶剂，去离子水为反溶剂，泊洛沙姆188作为表面活性剂，通过反溶剂法制备LE-NPs，采用单因素实验设计法优化LE-NPs制备工艺。并综合利用扫描电子显微镜、激光粒度仪、X射线衍射、差示扫描量热法等分析方法对获得的LE-NPs理化性质进行表征；采用气相色谱（GC）进行溶剂残留测定；并进行了体外溶出对比实验。结果 LE-NPs的最优制备条件为沉积时间10 min，叶黄素酯质量浓度50 mg/mL，溶剂反溶剂体积比为1∶7，泊洛沙姆188质量分数0.5%，搅拌速率950 r/min，沉积温度25 ℃；所得LE-NPs为球形，平均粒径为164 nm，其中四氢呋喃残留量为344.3 μg/g，低于人用药物注册技术要求国际协调会（ICH）要求的最低标准（0.780 mg/g）；在人工胃液环境中LE-NPs的饱和溶解度和溶出速率分别是原药的2.91倍和9.65倍。结论 反溶剂法制备的LE-NPs具有较好水溶性，在口服制剂中具有潜在的用途。

Objective To prepare lutein ester (LE) nanoparticles (LE-NPs) by anti-solvent method using tetrahydrofuran as solvent, deionized water as antisolvent and Poloxamer 188 as surfactant, and to optimize the process of getting LE-NPs. Methods The concentration of LE, ratio of solvent to solvent, type and dosage of surfactant, precipitation time and stirring speed were investigated factors affecting the particle size of LE-NPs. The raw LE and LE-NPs were observed and analyzed by scanning electron microscopy, laser particle size analyzer, X-ray diffraction, and differential scanning calorimetry; Solvent residue was tested by GC method. What's more, the solubility and dissolving capability of raw LE and LE-NPs also were detected in vitro in this study. Results The optimized preparation conditions of LE-NPs were as follows: 10 min of stirring time, 50 mg/mL of LE concentration, 1:7 of the volume ratio of solvent to antisolvent, 0.5% at mass fraction of poloxamer 188, 950 r/min of stirring speed, 25 ℃ of precipitation temperature. The mean particle size of spherical LE-NPs was 164 nm. XRD and DSC results showed that LE-NPs had lower crystallinity compared to raw drug, and mainly in amorphous state. The solvent residue result showed that tetrahydrofuran residue content in LE-NPs was 344.3 μg/g. Furthermore, the solubility and dissolution rate of LE-NPs were about 2.91 times and 9.65 times of raw LE. Conclusion LE-NPs prepared by antisolvent method could become a new formulation, which has higher solubility and bioavailability than raw LE.

国家自然科学基金资助项目（21473023）