Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression
Intramuscular delivery of DNA releasing microspheres: Microsphere properties and transgene expression
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DOI：
10.1016/j.jconrel.2006.01.013
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发表时间：
2006-05-01
影响因子：
10.8
通讯作者：
Shea, LD
中科院分区：
文献类型：
--
作者：
Jang, JH;Shea, LD
载质粒微球可以在靶组织中提供局部和持续的释放，因此有可能提高裸露DNA促进转基因表达的效率。在这份报告中，微球的设计参数是通过将转基因在肌肉内表达的程度和持续时间与聚合物分子量和交付的DNA质量相关联来进行研究的。采用低温复乳法制备聚(丙交酯-乙交酯)微球，并肌肉注射。以裸质粒团注为对照，肌肉细胞中转基因表达随时间逐渐降低。由低分子量聚合物制成的微球的表达水平从第一天到第92天增加，随后在第174天下降。减少微球的输送质量可以在同一时间内获得稳定的表达。然而，用高相对分子质量聚合物制备的微球只表达了14天。肌肉注射导致对微球的异物反应，这些邻近的浸润性细胞主要被转基因。这种对微球性质的了解决定了转基因表达和转基因细胞的分布，这可能有助于它们在组织工程或DNA疫苗等领域的应用。(C)2006爱思唯尔B.V.保留所有权利。
Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the mass of DNA delivered. Plasmid DNA was incorporated into poly (lactide-co-glycolide) microspheres using a cryogenic double emulsion process, and microspheres were injected intramuscularly. Bolus injection of naked plasmid was used for control, which exhibited transfection of muscle cells with transgene expression that g radually decreased over time. Microspheres fabricated from low molecular weight polymer had expression levels that increased from day I to day 92, which subsequently decreased through day 174. Decreasing the microsphere mass delivered resulted in steady expression during the same time. However, microspheres fabricated with high molecular weight polymer had expression for only 14 days. Intramuscular injection resulted in a foreign body response to the microspheres, and these infiltrating cells adjacent were primarily transfected. This understanding of microsphere properties that determine transgene expression and the distribution of transfected cells may facilitate their application to fields such as tissue engineering or DNA vaccines. (c) 2006 Elsevier B.V. All rights reserved.