期刊
BIOMATERIALS
卷 25, 期 1, 页码 147-157出版社
ELSEVIER SCI LTD
DOI: 10.1016/S0142-9612(03)00467-8
关键词
hyaluronic acid/hyaluronan; microsphere; DNA; gene transfer; selectin
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL065175] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL65175] Funding Source: Medline
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.
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