DNA delivery from photocrosslinked PEG hydrogels: encapsulation efficiency, release profiles, and DNA quality

被引:108
作者
Quick, DJ [1 ]
Anseth, KS [1 ]
机构
[1] Univ Colorado, Howard Hughes Med Inst, Dept Chem & Biol Engn, Boulder, CO 80309 USA
基金
美国国家卫生研究院;
关键词
controlled release; gene delivery; photopolymerization;
D O I
10.1016/j.jconrel.2004.01.021
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Sustained DNA delivery from polymer matrices provides a means for enhanced and prolonged gene therapy; however, limitations exist with respect to tailoring the DNA release profiles and maintaining the quality of the encapsulated DNA over time. To address these issues, PEG-based macromolecular monomers were photopolymerized to produce hydrogels with various degradation rates to control the DNA release profiles. Photocrosslinked PEG-based hydrogels were designed that released DNA for periods of 6-100 days with either nearly linear or delayed burst release profiles. Plasmid DNA was released primarily in the relaxed and supercoiled forms, and the released DNA showed high biological activity in plated cell cultures. The addition of both chemical and physical protective agents helped preserve the supercoiled form of the plasmid DNA during photoencapsulation (up to 75% compared to non-encapsulated plasmid controls), thereby enhancing the biological activity of the released DNA. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:341 / 351
页数:11
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