Hyaluronan microspheres for sustained gene delivery and site-specific targeting
Hyaluronan microspheres for sustained gene delivery and site-specific targeting
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DOI：
10.1016/s0142-9612(03)00467-8
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发表时间：
2004-01-01
期刊：
影响因子：
14
通讯作者：
Chen, WL
中科院分区：
文献类型：
--
作者：
Yun, YH;Goetz, DJ;Chen, WL
Hybryonan是一种天然存在的聚合物，在生物医学和化妆品应用中作为涂料、基质和水凝胶获得了广泛的成功。对于受控递送应用，将天然透明质酸配制成微球可能是有利的，但难以加工，除非使用有机溶剂或透明质酸已通过醚化改性。因此，我们提出了一种使用己二酰肼介导的交联化学制备透明质酸微球的新方法。为了评估它们的医学应用潜力，透明质酸微球与DNA结合用于基因递送或与抗原缀合用于细胞特异性靶向。结果表明，我们的方法，最初开发用于制备透明质酸水凝胶，产生强大的微球的尺寸分布为5-20妈妈。包封的质粒DNA的释放可以持续数月，并且能够在体外和体内转染。与E-和P-选择素的单克隆抗体偶联的Hybryonan微球显示出与表达这些受体的细胞的选择性结合。总之，我们已经开发了一种新的微球制剂，使用天然透明质酸，提供DNA在一个控制的速度和适应性位点特异性靶向。(C)2003 Elsevier Ltd.保留所有权利。
Hyaluronan is a naturally occurring polymer that has enjoyed wide successes in biomedical and cosmetic applications as coatings, matrices, and hydrogels. For controlled delivery applications, formulating native hyaluronan into microspheres could be advantageous but has been difficult to process unless organic solvents are used or hyaluronan has been modified by etherification. Therefore, we present a novel method of preparing hyaluronan microspheres using adipic dihydrazide mediated crosslinking chemistry. To evaluate their potential for medical applications, hyaluronan ruicrospheres are incorporated with DNA for gene delivery or conjugated with an antigen for cell-specific targeting. The results show that our method, originally developed for preparing hyaluronan hydrogets, generates robust microspheres with a size distribution of 5-20 mum. The release of the encapsulated plasmid DNA can be sustained for months and is capable of transfection in vitro and in vivo. Hyaluronan microspheres, conjugated with monoclonal antibodies to E- and P-selectin, demonstrate selective binding to cells expressing these receptors. In conclusion, we have developed a novel microsphere preparation using native hyaluronan that delivers DNA at a controlled rate and adaptable for site-specific targeting. (C) 2003 Elsevier Ltd. All rights reserved.