Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy
Paclitaxel loaded PEGylated gleceryl monooleate based nanoparticulate carriers in chemotherapy
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DOI：
10.1016/j.biomaterials.2012.06.056
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发表时间：
2012-10-01
期刊：
影响因子：
14
通讯作者：
Jain, Narendra K.
中科院分区：
文献类型：
--
作者：
Jain, Vikas;Swarnakar, Nitin K.;Jain, Narendra K.
为探索紫杉醇（PTX）在抗肿瘤治疗中的应用前景，以单油酸甘油酯（GMO）为载体，通过优化工艺参数，制备了紫杉醇（PTX）聚乙二醇化给药系统。通过偏光显微镜、透射电镜、原子力显微镜和小角X射线散射对所制备的体系进行了表征。由于基于GMO的LCNP表现出高溶血毒性和包封药物的更快释放（24小时内66.2 +/-2.5%），因此利用PEG化策略来增加血液相容性（溶血从60.3 +/-10.2%降低至4.4 +/-1.3%）并控制PTX的释放（24小时内释放43.6 +/-3.2%）。在MCF-7细胞系中评估了细胞毒性潜力和细胞摄取。此外，使用Tc-99 m-（锝放射性核素）标记的制剂在EAT（埃利希腹水瘤）荷瘤小鼠中进行生物分布研究，在24 h时，观察到PEG化载体的循环时间和肿瘤蓄积（分别为普通载体的14倍和8倍）增加。最后，进行肿瘤生长抑制实验，15天后，与初始肿瘤体积相比，对照组显示出15倍的肿瘤体积增强，而普通和PEG化系统分别仅显示出8倍和4倍的增强。结果表明，聚乙二醇化增强了基于转基因生物的系统的血液相容性和功效，该系统可作为紫杉醇的有效静脉给药载体。(C)2012爱思唯尔有限公司保留所有权利。
A PEGylated drug delivery system of paclitaxel (PTX), based on glyceryl monooleate (GMO) was prepared by optimizing various parameters to explore its potential in anticancer therapy. The prepared system was characterized through polarized light microscopy, TEM, AFM and SAXS to reveal its liquid crystalline nature. As GMO based LCNPs exhibit high hemolytic toxicity and faster release of entrapped drug (66.2 +/- 2.5% in 24 h), PEGylation strategy was utilized to increase the hemocompatibility (reduction in hemolysis from 60.3 +/- 10.2 to 4.4 +/- 1.3%) and control the release of PTX (43.6 +/- 3.2% released in 24 h). The cytotoxic potential and cellular uptake was assessed in MCF-7 cell lines. Further, biodistribution studies were carried out in EAT (Ehrlich Ascites tumor) bearing mice using Tc-99m-(Technetium radionuclide) labeled formulations and an enhanced circulation time and tumor accumulation (14 and 8 times, respectively) were observed with PEGylated carriers over plain ones, at 24 h. Finally, tumor growth inhibition experiment was performed and after 15 days, control group exhibited 15 times enhancement in tumor volume, while plain and PEGylated systems exhibited only 8 and 4 times enhancement, respectively, as compared to initial tumor volume. The results suggest that PEGylation enhances the hemocompatibility and efficacy of GMO based system that may serve as an efficient i.v. delivery vehicle for paclitaxel. (C) 2012 Elsevier Ltd. All rights reserved.