中文摘要：

目的制备具有较高载药量的蓝萼甲素（GLA）纳米混悬剂,并对其体内外性质进行研究。方法使用聚乳酸-羟基乙酸共聚物-聚乙二醇-聚乳酸-羟基乙酸共聚物（PLGA-PEG-PLGA）三嵌段聚合物为稳定剂,用溶剂沉淀联合高压匀质的方法制备蓝萼甲素纳米混悬剂。用动态光散射法测量蓝萼甲素纳米混悬剂粒径,透射电镜观察蓝萼甲素纳米粒的形态,透析法考察其体外释放,同时采用噻唑蓝（MTT）比色法评价蓝萼甲素纳米混悬剂对BGC和Hep G-2细胞的细胞毒性。用小动物活体成像监测包载DiR的蓝萼甲素纳米混悬剂在4T1肿瘤鼠内的分布。结果制备得到的蓝萼甲素纳米混悬剂的平均粒径为（222.6±4.32）nm、多分散度指数（PDI）为（0.237±0.016）,Zeta电位为（-11.5±0.954）mV;蓝萼甲素纳米混悬剂形态圆整呈球形,粒径分布均匀,载药量达（40.67±2.45）%,包封率为（69.11±3.02）%;体外释放显示,纳米粒能加速蓝萼甲素的溶出。蓝萼甲素溶液及纳米混悬剂对BGC细胞的IC50值分别为1.658和0.783 6μg·mL^-1,对HepG2细胞的IC50值分别为12.4和6.44μg·mL^-1,纳米混悬剂的抑瘤作用较原药提高1倍。从小动物活体成像的结果看出,蓝萼甲素纳米混悬剂在肿瘤部位有分布。结论成功制备了高载药量的蓝萼甲素纳米混悬剂,纳米制剂能有效提高蓝萼甲素的抗肿瘤活性,并有望成为其抗肿瘤应用的合适剂型。

英文摘要：

OBJECTIVE To prepare high drug loading glaucocalyxin A（GLA） nanosuspensions and study their properties in vitro.METHODS Using solvent precipitation combined with high pressure homogenization method,the GLA nanosuspensions were successfully prepared with PLGA-PEG-PLGA block copolymer being a stabilizer.The particle size of the resultant nanosuspensions was determined by dynamic light scattering（DLS）,their morphology was observed by transmission electron microscopy（TEM）,the crystalline state of GLA in the nanosuspensions was examined by differential scanning calorimetry（DSC）,and the in vitro release of GLA nanosuspensions was investigated using dialysis method.The in vitro anticancer cytotoxic activity of free GLA solution and GLA nanosuspensions against a gastric cancer cell line（BGC cells） and a hepatic cancer cell line（Hep G-2 cells） were performed using MTT assay.RESULTS GLA Nanosuspensions showed a mean particle size of（222.6 ± 4.32） nm,a polydispersity index（PDI） of（0.237 ± 0.016） and a Zeta potential of（-11.5 ± 0.954） mV.The average entrapment efficiency was（69.11 ± 3.02） % and the average drug loading was（40.67 ± 2.45） %.The particles in the nanosuspensions were spherical with smooth surface and uniform size distribution,and displayed sustained release in vitro.GLA nanosuspensions showed significant higher cytotoxicity than free GLA against BGC cells（IC50 value 0.784 μg · m L^-1vs.1.658 μg · m L^-1） and Hep G2 cells（IC50 value 12.4 μg ·m L^-1vs.6.44 μg· m L^-1）.CONCLUSION High drug loading GLA nanosuspensions are successfully prepared and well characterized in vitro.The resultant nanoparticles can efficiently enhance the antitumor activity of GLA and thus can be used as a suitable dosage form in this respect.