目的 制备不同粒径波棱甲素纳米混悬剂（herpetrione nanosuspension，Her-NS），并探讨粒径对Her-NS口服生物利用度的影响。方法 采用反溶剂沉淀法制备2种不同粒径Her-NS，采用单因素实验以平均粒径、多分散系数、稳定性指数为评价指标优化处方工艺参数，扫描电子显微镜（SEM）观察Her-NS形态，X射线衍射（XRD）分析晶型，透析法研究体外释放特性。通过SD大鼠比较2种不同粒径Her-NS口服药动学差异。结果 以P188、P407为稳定剂分别制备了200、450 nm 2种不同粒径Her-NS（Her-NS₂₀₀、Her-NS₄₅₀），SEM显示2种粒径的Her-NS均为球状，XRD分析表明2种粒径Her-NS均为无定型态。体外释放度与药动学结果显示，与波棱甲素原料药比较，2种粒径Her-NS的累积释放度明显提高，Her-NS的达峰浓度（C_max）、药时曲线下面积（AUC_0~t）均显著提高；Her-NS₂₀₀的C_max、AUC_0~t均高于Her-NS₄₅₀。结论 Her-NS可明显提高波棱甲素口服生物利用度，且粒径越小，生物利用度越高。

Objective To prepare herpetrione nanosuspension (Her-NS) with different particle sizes, and explore the effects of particle size on the oral bioavailability. Methods Her-NS with two different particle sizes were prepared by anti-solvent precipitation method, and optimized by single factor experiments with average particle size, polydispersity index, and stability index as evaluation indexes. The morphology of Her-NS was observed by scanning electron microscope (SEM), and the physical state was analyzed by X-ray diffraction (XRD). The drug release of Her-NS was evaluated by dialysis method. The oral pharmacokinetics of Her-NS with two different particle sizes were compared using SD rats. Results Her-NS with two different particle sizes around 200 nm (Her-NS₂₀₀) and 450 nm (Her-NS₄₅₀) were successfully prepared with P188 and P407 as stabilizers. SEM showed that Her-NS with two different particle sizes were all spherical in shape, and the XRD analysis showed that Her-NS with two different particle sizes were amorphous. In vitro release and pharmacokinetic results showed that the cumulative release and the C_max and AUC_0-t of Her-NS with two different particle sizes were significantly increased as compared to coarse Her, but the C_max and AUC_0-t of the Her-NS₂₀₀ were higher than those of Her-NS₄₅₀. Conclusion NS can significantly improve the oral bioavailability of Her, and the small particle size is more significant.

R283.6

国家自然科学基金资助项目（81573697）；国家自然科学基金资助项目（81873092）；国家重大新药创制（2016ZX09101073）