The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles.
The effect of hyperbranched polyglycerol coatings on drug delivery using degradable polymer nanoparticles.
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使用可降解的聚合物纳米颗粒的超支多甘油涂层对药物输送的影响。
DOI：
10.1016/j.biomaterials.2014.04.038
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发表时间：
2014-08
期刊：
影响因子：
14
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
--
作者：
Deng, Yang;Saucier-Sawyer, Jennifer K.;Hoimes, Christopher J.;Zhang, Junwei;Seo, Young-Eun;Andrejecsk, Jillian W.;Saltzman, W. Mark
用于医学的纳米颗粒的一个关键属性是能够避免被肝脏和其他组织中的吞噬细胞快速摄取。几十年来，聚乙二醇(PEG)涂料一直是这方面的黄金标准。在这里，我们研究了超支化聚甘油(HPG)作为NPs的替代涂层。在早期的工作中，HPG用胺修饰，然后连接到聚乳酸(PLA)上，但这种方法削弱了HPG抵抗生物分子非特异性吸附的能力。取而代之的是，我们通过一步酯化反应合成了聚乳酸-羟丙基葡萄糖共聚物。用聚乳酸-羟丙基葡萄糖单乳液制得NPS：荧光染料或抗肿瘤药物喜树碱(CPT)被高效包裹在纳米粒中。将聚乳酸-羟丙基葡萄糖纳米粒与聚乳酸-聚乙二醇纳米粒进行定量比较，后者使用的方法已经为人体药物输送进行了广泛的优化。尽管在大小、药物释放情况和体外细胞毒性方面相似，但聚乳酸-羟丙基葡萄糖纳米粒比聚乳酸-聚乙二醇纳米粒的血液循环时间显著延长，肝脏蓄积显著减少。与CPT负载的聚乳酸-聚乙二醇纳米粒相比，CPT-PLAHPG纳米粒具有更高的悬浮稳定性和更好的体内抗肿瘤疗效。我们的结果表明，HPG作为纳米粒的表面涂层在药物传递方面优于聚乙二醇。
A key attribute for nanoparticles (NPs) that are used in medicine is the ability to avoid rapid uptake by phagocytic cells in the liver and other tissues. Poly(ethylene glycol) (PEG) coatings has been the gold standard in this regard for several decades. Here, we examined hyperbranched polyglycerols (HPG) as an alternate coating on NPs. In earlier work, HPG was modified with amines and subsequently conjugated to poly(lactic acid) (PLA), but that approach compromised the ability of HPG to resist non-specific adsorptions of biomolecules. Instead, we synthesized a copolymer of PLA-HPG by a one-step esterification. NPs were produced from a single emulsion using PLA-HPG: fluorescent dye or the anti-tumor agent camptothecin (CPT) were encapsulated at high efficiency in the NPs. PLA-HPG NPs were quantitatively compared to PLA-PEG NPs, produced using approaches that have been extensively optimized for drug delivery in humans. Despite being similar in size, drug release profile and in vitro cytotoxicity, the PLA-HPG NPs showed significantly longer blood circulation and significantly less liver accumulation than PLA-PEG. CPT-loaded PLA-HPG NPs showed higher stability in suspension and better therapeutic effectiveness against tumors in vivo than CPT-loaded PLA-PEG NPs. Our results suggest that HPG is superior to PEG as a surface coating for NPs in drug delivery.
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影响因子：
4.9
作者：
Li, Shyh-Dar;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
1.2
作者：
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影响因子：
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作者：
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通讯作者：
Burt, Helen M.
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作者：
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通讯作者：
Brooks, Donald Elliott
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作者：
Cheng, Jianjun;Teply, Benjamin A.;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.