摘要
目的:制备白屈菜红碱纳米粒(CHE-NPs),对其处方进行优化,并评价其体外释药行为及对黑色素瘤的抑制作用。方法:以甲氧基聚乙二醇-聚乳酸-羟基乙酸共聚物(m PEG-PLGA)为载体材料,采用纳米沉淀法制备CHE-NPs,采用高效液相色谱法和透析袋法测定包封率、载药量。以二者的总评归一(OD)值为因变量,以CHE投药量、mPEG-PLGA质量浓度、泊洛沙姆188(F68)浓度为自变量,采用Box-Behnken响应面设计优化CHE-NPs处方。检测最优处方所制CHE-NPs的粒径和Zeta电位,考察其体外释药特征,比较CHE原料药和CHE-NPs对小鼠B16黑色素瘤细胞存活率的影响并计算二者的半数抑制浓度。结果:最优处方为CHE投药量2 mg、mPEG-PLGA质量浓度13 mg/mL、F68浓度1.8%。以此所制CHE-NPs的平均包封率为(80.18±1.11)%,平均载药量为(11.36±0.28)%,平均OD值为0.96±0.04[与OD预测值(0.90)的相对偏差为6.67%],粒径为(113.1±1.40)nm,Zeta电位为(-21.6±0.29)m V,多分散性指数为0.07±0.01(n=3)。CHE对照品、CHE-NPs在孵育8 h时的累积释放率分别为90.87%、68.68%,后者的体外释药行为符合Weibull动力学模型。CHE-NPs对B16黑色素瘤细胞的抑制作用显著强于CHE原料药,CHENPs和CHE原料药的24 h半数抑制浓度分别为69.35、107.36μg/mL。结论:所制CHE-NPs具有缓释作用和较强的载药能力,同时增强了CHE对黑色素瘤的体外抑制作用。
OBJECTIVE:To prepare chelerythrine nanoparticles(CHE-NPs),optimize their formulation,and evaluate its drug release behavior in vitro and its inhibitory effect on melanoma.METHODS:Using methoxy polyethylene glycol-poly(lactic-coglycolic acid)(mPEG-PLGA)as carrier,CHE-NPs were prepared by the nano-precipitation method.HPLC method and dialysis bag method were used to determine entrapment efficiency and drug loading.The formulation of CHE-NPs was optimized by BoxBehnken response surface design using overall desirability(OD) of them as dependent variables,CHE dosage,mPEG-PLGA concentration and poloxamer 188(F68)concentration as independent variables.The particle size and Zeta potential of CHE-NPs prepared by the optimal formulation were detected;the characteristics of drug release in vitro were investigated;the effects of CHE and CHE-NPs on survival rate of mice B16 melanoma cells were compared,and median inhibition concentrations(IC50)of them were calculated.RESULTS:The optimal formulation included CHE of 2 mg,mPEG-PLGA of 13 mg/mL,F68 of 1.8%.Average entrapment efficiency rate of CHE-NPs prepared by the optimal formulation was(80.18 ± 1.11)%,average drug loading was(11.36±0.28)%,average OD value was 0.96±0.04 [the relative deviation from predicted value(0.90)of OD was 6.67%];particle size was(113.1±1.40)nm,and Zeta potential was(-21.6±0.29)mV;polydispersity index was 0.07±0.01(n=3);accumulative release rates of CHE control and CHE-NPs were 90.87% and 68.68% within 8 h,and drug release behavior in vitro of the latter was in accordance with Weibull kinetic model.Inhibitory effect of CHE-NPs on B16 melanoma cells was significantly stronger than that of CHE;the 24 h IC50 of CHE-NPs and CHE were 69.35 and 107.36 μg/m L,respectively.CONCLUSIONS:The prepared CHE-NPs show good sustained-effect and high capacity of drug loading,and strengthen the inhibitory effect of CHE on melanoma.
作者
杨锦
韩伟
张永萍
陈晓兰
李哲
刘杰
吴静澜
YANG Jin;HAN Wei;ZHANG Yongping;CHEN Xiaolan;LI Zhe;LIU Jie;WU Jinglan(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;College of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Innovation Research and Development Center of Veterinary Traditional Chinese Medicine Preparations,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
出处
《中国药房》
CAS
北大核心
2021年第24期2980-2986,共7页
China Pharmacy
基金
国家苗药工程技术研究中心组建项目(No.2014FU-125Q09)
贵州省科技厅学术新苗培养及创新探索专项项目(No.黔科合平台人才[2018]5766号-13)
地方病与少数民族性疾病教育部重点实验室(贵州医科大学)开放课题基金资助项目(No.黔教合KY字[2019]047)。
作者简介
杨锦,硕士研究生。研究方向:中药及民族药物新制剂与新剂型。E-mail:1510428733@qq.com;通信作者:吴静澜,教授,硕士生导师,硕士。研究方向:中药及民族药物新制剂与新剂型。E-mail:1259803072@qq.com。
