Nanoparticles of poly(lactide) - Tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers for protein drug delivery
Nanoparticles of poly(lactide) - Tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers for protein drug delivery
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DOI：
10.1016/j.biomaterials.2007.01.003
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发表时间：
2007-04-01
期刊：
影响因子：
14
通讯作者：
Feng, Si-Shen
中科院分区：
文献类型：
--
作者：
Lee, Sie Huey;Zhang, Zhiping;Feng, Si-Shen
以牛血清白蛋白（BSA）为模型蛋白，采用复乳法制备了不同比例的聚乳酸-生育酚聚乙二醇琥珀酸酯（PLA-TPGS）共聚物纳米粒。考察了PLA：TPGS组分比和BSA负载量对药物包封率和体外释药行为的影响。PLA-TPGS纳米粒实现了16.7%的蛋白载药量和75.6%的EE，其表现出受控蛋白释放的双相模式，对于TPGS含量更多的那些纳米粒具有更高的初始突释。此外，释放的蛋白质在37 ℃下保持良好的结构完整性至少35天，如十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和圆二色性（CD）光谱所示。与其他可生物降解的聚合物纳米粒子如聚乳酸-乙交酯（PLGA）纳米粒子相比，聚乳酸-TPGS纳米粒子可以为蛋白质提供一个更温和的环境。共聚焦激光扫描显微镜（CLSM）观察证实NIH-3 T3成纤维细胞和Caco-2癌细胞对PLA-TPGS NP的细胞内摄取。该研究表明PLA-TPGS纳米粒在蛋白质和肽的临床制剂中具有巨大的潜力。(c)2007爱思唯尔有限公司保留所有权利。
Nanoparticles (NPs) of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers with various PLA:TPGS component ratios were prepared by the double emulsion technique for protein drug formulation with bovine serum albumin (BSA) as a model protein. Influence of the PLA:TPGS component ratio and the BSA loading level on the drug encapsulation efficiency (EE) and in vitro drug release behavior was investigated. The PLA-TPGS NPs achieved 16.7% protein drug loading and 75.6% EE, which exhibited a biphasic pattern of controlled protein release with higher initial burst for those NPs of more TPGS content. Furthermore, the released proteins retained good structural integrity for at least 35 days at 37 degrees C as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy. Compared with other biodegradable polymeric NPs such as POIY(D,L-lactide-co-glycolide) (PLGA) NPs, PLA-TPGS NPs could provide the encapsulated proteins a milder environment. Confocal laser scanning microscopy (CLSM) observation demonstrated the intracellular uptake of the PLA-TPGS NPs by NIH-3T3 fibroblast cells and Caco-2 cancer cells. This research suggests that PLA-TPGS NPs could be of great potential for clinical formulation of proteins and peptides. (c) 2007 Elsevier Ltd. All rights reserved.