Covalent conjugation of polyethyleneimine on biodegradable microparticles for delivery of plasmid DNA vaccines
Covalent conjugation of polyethyleneimine on biodegradable microparticles for delivery of plasmid DNA vaccines
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DOI：
10.1016/j.biomaterials.2005.03.043
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发表时间：
2005-11-01
期刊：
影响因子：
14
通讯作者：
Roy, K
中科院分区：
文献类型：
--
作者：
Kasturi, SP;Sachaphibulkij, K;Roy, K
近年来，鉴于提高DNA疫苗接种的效力，基于微粒的核酸递送获得了特别的关注。已经通过将pDNA包封在可生物降解的微粒内或通过阳离子微粒上的表面吸附报道了这种改善。然而，在DNA疫苗的递送系统的合理设计中，基因递送至抗原呈递细胞（APC）的内在细胞内屏障尚未得到充分解决。在这里，我们报告了可生物降解的微粒的合成和表征，其（a）可以被动地靶向吞噬APC，（B）具有可能允许增强的粘粒逃逸的内在缓冲能力，（c）没有细胞毒性，以及（d）具有改善的APC转染效率。使用碳二亚胺化学将支链聚乙烯亚胺（b-PEI）共价缀合至聚（丙交酯-共乙交酯）（PLGA）微粒的表面，以产生能够在单一可注射递送载体内同时递送DNA疫苗以及其它免疫调节剂（细胞因子或核酸）的阳离子微粒。我们的研究结果表明，共价结合的b-PEI允许有效的表面负载的核酸，引入固有的缓冲特性的PLGA颗粒和增强吞噬细胞的转染，而不影响PLGA载体的细胞相容性。(c)2005爱思唯尔有限公司保留所有权利。
Microparticle-based delivery of nucleic acids has gained particular attention in recent years in view of improving the potency of DNA vaccination. Such improvement has been reported by encapsulation of pDNA within biodegradable microparticles or through surface adsorption on cationic microparticles. However, the intrinsic intracellular barriers for gene delivery to antigen presenting cells (APCs) have not been adequately addressed in the rational design of delivery systems for DNA vaccines. Here we report synthesis and characterization of biodegradable microparticles that (a) can passively target phagocytic APCs, (b) have intrinsic buffering ability that might allow for enhanced pliagosomal escape, (c) are not cytotoxic and (d) have improved APC transfection efficiency. Branched polyethyleneimine (b-PEI) was covalently conjugated using carbodiimide chemistry to the surface of poly(lactide-coglycolide) (PLGA) microparticles to create cationic microparticles capable of simultaneously delivering both DNA vaccines as well as other immunomodulatory agents (cytokines or nucleic acids) within a single injectable delivery vehicle. Our results indicate that covalent Conjugation of b-PEI allows efficient surface loading of nucleic acids, introduces intrinsic buffering properties to PLGA particles and enhances transfection of phagocytic cells without affecting the cytocompatibility of PLGA carriers. (c) 2005 Elsevier Ltd. All rights reserved.