Gene delivery nanoparticles fabricated by supercritical fluid extraction of emulsions.
Gene delivery nanoparticles fabricated by supercritical fluid extraction of emulsions.
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DOI：
10.1016/j.ijpharm.2009.12.024
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发表时间：
2010-03-15
影响因子：
5.8
通讯作者：
Kompella, Uday B.
中科院分区：
文献类型：
--
作者：
Mayo, Aaron S.;Ambati, Balamurali K.;Kompella, Uday B.
非病毒聚合物基因递送系统提供增加的保护免受核酸酶降解、增强的质粒DNA（pDNA）摄取和受控的剂量以维持pDNA施用的持续时间。这样的基因递送系统可以由生物相容性和生物可降解的聚合物如聚（d，l-乳酸-共-乙醇酸）（PLGA）配制。亲水性大分子如pDNA的实验负载在聚合物颗粒中是低的。本研究的目的是建立一种基于CO2的超临界流体萃取乳液（SFEE）工艺，以制备具有高质粒负载量和负载效率的pEGFP-PLGA纳米粒。另一个目的是确定pFlt 23 k（一种能够抑制血管内皮生长因子（VEGF）分泌的抗血管生成pDNA）在使用SFEE方法形成纳米颗粒后的功效。结果表明，SFEE方法允许高的pDNA实际负载（19.7%w/w）、高负载效率（> 98%）和低残留溶剂（< 50 ppm），这是由于SFEE方法提供的有效溶剂去除导致的快速颗粒形成。pFlt 23 K-PLGA纳米颗粒能够体外转染，在常氧和缺氧条件下显著减少人肺泡上皮细胞（A549）分泌的VEGF。pFlt 23 K-PLGA纳米颗粒没有表现出细胞毒性，并且在治疗VEGF水平升高的新生血管疾病中具有潜在价值。
Non-viral polymeric gene delivery systems offer increased protection from nuclease degradation, enhanced plasmid DNA (pDNA) uptake, and controlled dosing to sustain the duration of pDNA administration. Such gene delivery systems can be formulated from biocompatible and biodegradable polymers such as poly (d,l-lactic-co-glycolic) acid (PLGA). Experimental loading of hydrophilic macromolecules such as pDNA is low in polymeric particles. The study purpose was to develop a supercritical fluid extraction of emulsions (SFEE) process based on CO2 for preparing pEGFP-PLGA nanoparticles with high plasmid loading and loading efficiency. Another objective was to determine the efficacy of pFlt23k, an anti-angiogenic pDNA capable of inhibiting vascular endothelial growth factor (VEGF) secretion, following nanoparticle formation using the SFEE process. Results indicated that the SFEE process allows high actual loading of pDNA (19.7% w/w), high loading efficiency (> 98%), and low residual solvents (< 50 ppm), due to rapid particle formation from efficient solvent removal provided by the SFEE process. pFlt23K-PLGA nanoparticles were capable of in vitro transfection, significantly reducing secreted VEGF from human lung alveolar epithelial cells (A549) under normoxic and hypoxic conditions. pFlt23K-PLGA nanoparticles did not exhibit cytotoxicity and are of potential value in treating neovascular disorders wherein VEGF levels are elevated.
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影响因子：
3.8
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通讯作者：
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