目的 制備番荔枝總內(nèi)酯納米混懸劑，并對其體外抗腫瘤作用進行研究。方法 使用反溶劑沉淀法中的超聲法制備番荔枝總內(nèi)酯納米混懸劑，考察其處方和制備工藝參數(shù)；動態(tài)光散射法測定其粒徑和電位，透射電鏡考察其粒徑分布和形態(tài)；并對其人工胃腸液穩(wěn)定性進行考察；采用MTT比色法比較番荔枝總內(nèi)酯納米混懸劑和溶液對HepG2細胞毒性差異。結(jié)果 制備方法為將10 mg番荔枝總內(nèi)酯與1 mg PGDA共溶于1 mL有機溶劑中，超聲（250 W）快速注入到5 mL水中，減壓旋轉(zhuǎn)蒸發(fā)除去有機溶劑，調(diào)整總體積至5 mL。番荔枝總內(nèi)酯納米混懸劑平均粒徑為（146.0±2.4）nm，多分散指數(shù)（PDI）為0.184±0.02，Zeta電位（26.0±2.0）mV，納米混懸劑幾乎呈類球型，粒徑分布接近于正態(tài)分布，分布比較均勻；人工胃腸液內(nèi)4 h穩(wěn)定存在，粒徑基本不發(fā)生變化；對HepG2細胞增殖均有一定的抑制作用，番荔枝總內(nèi)酯納米混懸劑組的細胞增殖抑制效果均優(yōu)于溶液組。結(jié)論 制備了以PGDA為載體的番荔枝總內(nèi)酯納米混懸劑，解決了藥物的難溶和給藥問題，為番荔枝總內(nèi)酯的納米劑型研究提供了參考。

Objective To prepare Annonaceous Acetogenins (ACGs) Naonosuspensions and study its anti-tumor activities in vitro. Methods ACGs Naonosuspensions were prepared with ultrasonic method in anti-solvent precipitation and its prescription and preparation process parameters were investigated. Dynamic light scattering method was used to measure particle size and transmission electron microscopy was used to observe the morphology. The stability of ACGs Nanosuspensions in different medium was also studied. MTT assay was used to assess their in vitro cytotoxicity against HepG2 cell line in contrast to free ACGs. Results The best preparation method was as following:10 mg ACGs and 1 mg PGDA co-dissolved in 1 mL organic solvents, and then were rapidly infused into 5 mL water by ultrasound (250 W), then decompressed and rotated evaporation to remove organic solvents, and were adjusted the total volume to 5 mL. The average particle size of ACGs Naonosuspensions was (146.0 ±2.4) nm, the polydispersity index (PDI) value was 0.184 ±0.02, the Zeta potential was (26.0 ±2.0) mV, and the particle size distribution was close to normal distribution. Naonosuspensions were nearly spherical, and the distribution was more uniform. They were quite stable in artificial gastric juice and intestinal juice for 4 h. ACGs Naonosuspensions had a certain inhibitory effect against proliferation of HepG2 cells, and the effect of naonosuspensions group was better than that of the solution group. Conclusion ACGs Naonosuspensions are successfully prepared taking PGDA as the carrier, and insolubility and drug delivery are solved, which provides reference for nano-formulation study of ACGs.

國家自然科學基金-廣東聯(lián)合基金資助項目（U1401223）