Yun Yang H, Goetz Douglas J, Yellen Paige, Chen Weiliam
Department of Biomedical Engineering, State University of New York, 348 Psychology A Building, Stony Brook, NY 11794-2580, USA.
Biomaterials. 2004 Jan;25(1):147-57. doi: 10.1016/s0142-9612(03)00467-8.
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 microspheres 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 hydrogels, generates robust microspheres with a size distribution of 5-20mum. 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.
透明质酸是一种天然存在的聚合物，作为涂层、基质和水凝胶在生物医学和化妆品应用中取得了广泛成功。对于控释应用，将天然透明质酸制成微球可能具有优势，但除非使用有机溶剂或通过醚化对透明质酸进行改性，否则很难加工。因此，我们提出了一种使用己二酸二酰肼介导的交联化学制备透明质酸微球的新方法。为了评估它们在医学应用中的潜力，将透明质酸微球与DNA结合用于基因传递，或与抗原偶联用于细胞特异性靶向。结果表明，我们最初为制备透明质酸水凝胶而开发的方法能够生成尺寸分布为5-20μm的坚固微球。封装的质粒DNA的释放可以持续数月，并且能够在体外和体内进行转染。与E-选择素和P-选择素单克隆抗体偶联的透明质酸微球表现出对表达这些受体的细胞的选择性结合。总之，我们开发了一种使用天然透明质酸的新型微球制备方法，该方法能够以可控速率递送DNA并适用于位点特异性靶向。
