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AEYLR小肽修饰的紫杉醇纳米结构脂质载体的制备及抗肿瘤效果评价 被引量:3

Preparation of Small Peptide AEYLR Modified Paclitaxel Nanostructured Lipid Carriers and Evaluation of Its Anti-tumor Effects
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摘要 目的:制备序列为丙氨酸-谷氨酸-酪氨酸-亮氨酸-精氨酸(简称为"AEYLR")的小肽修饰的紫杉醇(PTX)纳米结构脂质载体(A-P-NLC),并对其体内外抗肿瘤效果进行评价。方法:采用熔融乳化-低温固化法制备纳米结构脂质载体(NLC)、PTX纳米结构脂质载体(P-NLC)和A-P-NLC,表征其外观形态、粒径、多分散指数(PDI)、Zeta电位,并检测其包封率、载药量及体外释放度;以NCI-H1299细胞和S180细胞为对象,采用CCK-8法对游离PTX、P-NLC、A-P-NLC(0.44~44.00μg/mL,以PTX计)的细胞抑制作用进行考察,并计算其半数抑制浓度(IC50);以S180荷瘤小鼠为模型动物,对游离PTX、P-NLC、A-P-NLC(5 mg/kg,以PTX计)的抑瘤效果进行评价。结果:P-NLC和A-P-NLC外观均呈类圆形、分布均匀;A-P-NLC的粒径、PDI、Zeta电位分别为(43.92±0.76)nm、0.203±0.034、(-19.77±1.16)m V,较P-NLC有所增加;A-P-NLC的包封率、载药量分别为(95.71±0.68)%、(1.97±0.25)%,较P-NLC有所降低;A-P-NLC在48 h内累积释放百分率达(35.17±2.08)%,较游离PTX表现出明显的缓释作用,且比P-NLC的释放更缓慢。与游离PTX和P-NLC比较,相同质量浓度的A-P-NLC对NCI-H1299细胞和S180细胞的抑制率大部分均显著升高,IC50值均显著降低;A-P-NLC给药处理的S180荷瘤小鼠无死亡现象,一般状态良好,且瘤体积显著缩小、瘤质量显著降低、瘤质量抑制率显著升高(P<0.05或P<0.01)。结论:A-P-NLC具有明显的缓释作用,其对NCI-H1299细胞和S180细胞的体外抑制作用以及对小鼠S180实体瘤的抑制作用均优于游离PTX和P-NLC,且毒性有所降低。 OBJECTIVE:To prepare Paclitaxel(PTX)nanostructured lipid carriers(NLC)modified by small peptide alanine-glutamic acid-tyrosine-leucine-arginine(AEYLR),and to evaluate its anti-tumor effect in vitro and in vivo.METHODS:NLC,PTX-NLC(P-NLC)and AEYLR modified P-NLC(A-P-NLC)were prepared by emulsion evaporation-low temperature solidification curing method.Its appearance,particle size,multi-dispersion index(PDI)and Zeta potential were characterized,encapsulation rate,drug loading and in vitro drug release were detected respectively.Using NCI-H1299 and S180 cells as objects,CCK-8 method was adopted to investigate inhibitory effects of free PTX,P-NLC and A-P-NLC(0.44-44.00μg/mL,by PTX)to those cells.The half inhibition concentration(IC50)was calculated.Using S180 tumor-bearing mice as model animal,anti-tumor effects of free PTX,P-NLC and A-P-NLC(5 mg/kg,by PTX)were evaluated.RESULTS:P-NLC and A-P-NLC were round-like and dispersed evenly.The particle size,PDI and Zeta potential of A-P-NLC were(43.92±0.76)nm,0.203±0.034 and(-19.77±1.16)mV,which were all increased to certain extent,compared with P-NLC.The encapsulation efficiency and drug loading of A-P-NLC were(95.71±0.68)%and(1.97±0.25)%,which were both decreased to certain extent,compared with P-NLC.The cumulative release rate of A-P-NLC was(35.17±2.08)%within 48 h,showing significant sustained-release effect compared with free PTX;the release of A-P-NLC was slower than P-NLC.Compared with free PTX and P-NLC,inhibitory rates of same concentration of A-P-NLC to NCI-H1299 cells and S180 cells were almost increased significantly,while IC50 values were all decreased significantly.There was no death in S180 tumor-bearing mice treated with A-P-NLC and the general condition was good;the volume of tumors was significantly reduced,the mass of tumors was significantly reduced,and the inhibition rate of tumors was significantly increased(P<0.05 or P<0.01).CONCLUSIONS:A-P-NLC has significantly sustained-release effects;its inhibitory rate to NCI-H1299 cells and S180 cells in vitro,and its inhibitory effects on S180 solid tumor in mice are all better than free PTX and P-NLC,while the toxicity is decreased to certain extent.
作者 韩翠艳 周建文 刘畅 马晓星 袁橙 董岩 金珊珊 HAN Cuiyan;ZHOU Jianwen;LIU Chang;MA Xiaoxing;YUAN Cheng;DONG Yan;JIN Shanshan(School of Pharmacy,Qiqihar Medical College,Heilongjiang Qiqihar 161006,China;School of Pharmacy,Jiamusi University,Heilongjiang Jiamusi 154007,China;Dept.of Preparation,Beijing Wanquan DezhongPharmaceutical Technology Co.,Ltd.,Beijing 102299,China)
出处 《中国药房》 CAS 北大核心 2019年第6期770-775,共6页 China Pharmacy
基金 黑龙江省自然科学基金面上项目(No.H2015070)
关键词 AEYLR 小肽 紫杉醇 纳米结构脂质载体 抗肿瘤 小鼠 AEYLR Small peptide Paclitaxel Nanostructured lipid carriers Anti-tumor Mice
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