维生素C磷脂复合物及其纳米粒的制备、表征及体外抗肿瘤活性考察  

Preparation,Characterization and in vitro Antitumor Activity of Vitamin C Phospholipid Complex and Its Nanoparticles

作　　者：姚秋娥[1] 石三军[2] 周敏[2] 卢来春[2] 赵语[1] 

机构地区：[1]重庆医科大学附属大学城医院药剂科,重庆401331 [2]第三军医大学大坪医院野战外科研究所药剂科,重庆400042

出　　处：《中国医药工业杂志》2016年第11期1408-1413,共6页Chinese Journal of Pharmaceuticals

摘　　要：采用磷脂复合物提高维生素C(1)的脂溶性和稳定性。以复合率为指标,通过单因素试验优化得到1磷脂复合物(SPC-1)的制备工艺为:将投料质量比为12∶1的大豆磷脂和1溶于反应溶剂无水乙醇中,使1浓度为1 g/L,于45℃反应1 h。照优化工艺制备的SPC-1复合率高达92.5%。进一步采用紫外(UV)、红外(FT-IR)、差示扫描量热(DSC)和X射线衍射(XRD)等方法进行表征,并考察了1及其复合物的溶解度和油水分配系数。结果表明,1磷脂复合物在不同介质中的溶解度和表观油水分配系数均比1原料药高。在此基础上制备了基于SPC-1的固体脂质纳米粒(SPC-1-NPs),其包封率为(56.6±0.6)%,显著高于1固体脂质纳米粒(1-NPs)的包封率[(6.8±1.0)%]。体外试验显示,1原料药、SPC-1、1-NPs和SPC-1-NPs对黑素瘤癌B16F10细胞的IC_(50)值分别为115.41、11.49、8.03和2.73mg/ml,可见SPC-1-NPs的体外抗肿瘤活性最强。The phospholipid complex was prepared to improve the liposolubility and stability of vitamin C （1）. The formulation and preparation process of the l-loaded phospholipid complex （SPC-1） were optimized by single factor test with combining ratio as the index. The optimal preparation of SPC-1 was as follows： the soybean phospholipid and 1 in mass ratio of 12 ：1 were solved in absolute ethanol to ensure that the final concentration of 1 reached 1 g/L, then the reaction was carried out at 45℃ for 1 h. The combining ratio of the optimal SPC-1 was 92.5 %. Furthermore, the physicochemical properties of the SPC-1 were characterized by ultraviolet spectroscopy （UV）, Fourier transform infrared spectroscopy （FT-IR）, differential scanning calorimetry （DSC） and X-ray diffraction （XRD）. The solubilities and appearance oil-water distribution coefficients （Papp） of the bulk drug 1 and SPC-1 were determined respectively. The results showed that the solubilities and Papp values of SPC-1 in different media were all higher than those of 1. Then the solid lipid nanoparticles based on the optimal SPC-1, named as SPC-1-NPs, were prepared. The entrapment efficiencies of the SPC-I-NPs and the solid lipid nanoparticles loaded with 1 （1-NPs） were （56.6±0.6） % and （6.84-1.0） %, showing a significant difference. The IC50 values of bulk drug 1, SPC-1, 1-NPs and SPC-1-NPs against melanoma B16F10 cells were 115.41, 11.49, 8.03 and 2.73 μg/ml, respectively. It indicated that the in vitro antitumor activity of SPC-1-NPs was the strongest among them.

关 键 词：磷脂复合物 维生素C 固体脂质纳米粒 理化性质 溶解度 表观油水分配系数 体外抗肿瘤活性 

分 类 号：R944.9[医药卫生—药剂学]