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
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篇名: 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
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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(0.44~44.00 μg/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)mV,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。
ABSTRACT: 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 (0.44-44.00 μg/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.
期刊: 2019年第30卷第6期
作者: 韩翠艳,周建文,刘畅,马晓星,袁橙,董岩,金珊珊
AUTHORS: HAN Cuiyan,ZHOU Jianwen,LIU Chang,MA Xiaoxing,YUAN Cheng,DONG Yan,JIN Shanshan
关键字: AEYLR;小肽;紫杉醇;纳米结构脂质载体;抗肿瘤;小鼠
KEYWORDS: AEYLR; Small peptide; Paclitaxel; Nano- structured lipid carriers; Anti-tumor; Mice
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