Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS)
Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS)
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DOI：
10.1016/j.jconrel.2007.03.006
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发表时间：
2007-06-22
影响因子：
10.8
通讯作者：
Amiji, Mansoor M.
中科院分区：
文献类型：
--
作者：
Bhavsar, Mayank D.;Amiji, Mansoor M.
本研究的目的是开发和评估一种新型的纳米微球口服系统（NiMOS）的基因递送和转染在胃肠道（GI）的特定区域。将编码β-半乳糖苷酶（CMV-β gal）或增强型绿色荧光蛋白（EFGP-N1）的质粒DNA包封在B型明胶纳米颗粒中。NiMOS通过进一步保护聚（ε-己内酯）（PCL）基质中的DNA-负载的纳米颗粒以形成直径小于5.0 μ m的微球来制备。为了评价经口给药后的生物分布，将放射性标记（In-111标记）明胶纳米颗粒和NiMOS经口给予禁食Wistar大鼠。生物分布研究的结果表明，虽然明胶纳米颗粒相当快地穿过胃肠道，在第一个小时内超过85%的每克给药剂量位于大肠中，但NiMOS在胃和小肠中停留的时间相对较长。在对照和试验制剂中以100 μ g剂量经口给予CMV-β gal或EFGP-N1质粒DNA后，本研究中给出的定性结果为经口给予NiMOS的转染能力提供了概念验证。给药后5天，我们观察到转基因在大鼠小肠和大肠中的表达。基于这些初步结果，NiMOS显示出作为用于治疗和疫苗接种目的的新型基因递送载体的显著潜力。(c)2007 Elsevier B. V.保留所有权利。
The aim of this investigation was to develop and evaluate a novel nanoparticles-in-microsphere oral system (NiMOS) for gene delivery and transfection in specific regions of the gastrointestinal (GI) tract. Plasmid DNA, encoding either for beta-galactosidase (CMV-beta gal) or enhanced green fluorescent protein (EFGP-N1), was encapsulated in type B gelatin nanoparticles. NiMOS were prepared by further protecting the DNA-loaded nanoparticles in a poly(epsilon-caprolactone) (PCL) matrix to form microspheres of less than 5.0 mu m in diameter. In order to evaluate the biodistribution following oral administration, radiolabeled (In-111-labeled) gelatin nanoparticles and NiMOS were administered orally to fasted Wistar rats. The results of biodistribution studies showed that, while gelatin nanoparticles traversed through the GI tract fairly quickly with more than 85% of the administered dose per gram localizing in the large intestine within the first hour, NiMOS resided in the stomach and small intestine for relatively longer duration. Following oral administration of CMV-beta gal or EFGP-N1 plasmid DNA at 100 mu g dose in the control and test formulations, the qualitative results presented in this study provide the proof-of-concept for the transfection capability of NiMOS upon oral administration. After 5 days post-administration, we observed transgene expression in the small and large intestine of rats. Based on these preliminary results, NiMOS show significant potential as novel gene delivery vehicle for therapeutic and vaccination purposes. (c) 2007 Elsevier B.V. All rights reserved.