Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation
Controlled release of plasmid DNA from cationized gelatin hydrogels based on hydrogel degradation
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DOI：
10.1016/s0168-3659(02)00026-3
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发表时间：
2002-04-23
影响因子：
10.8
通讯作者：
Tabata, Y
中科院分区：
文献类型：
--
作者：
Fukunaka, Y;Iwanaga, K;Tabata, Y
通过引入乙二胺对明胶进行阳离子化，制备的明胶通过不同浓度的戊二醛交联得到阳离子化明胶（CG）水凝胶作为质粒DNA的载体，实现了质粒DNA的体内控释和基因表达调控。比较了CG水凝胶中质粒DNA的体内释放和水凝胶的体内降解。将含有i -125标记质粒DNA的CG水凝胶植入小鼠股肌后，质粒DNA的残留放射性随时间的延长而降低，保留期随水凝胶含水量的减少而延长。i -125标记的CG水凝胶含水量越高，水凝胶放射性随时间降低的速度越快。无论水凝胶的含水量如何，质粒DNA在水凝胶中停留的时间谱与水凝胶放射性的时间谱基本一致。肌内植入含有CG水凝胶的质粒DNA可显著增强植入部位周围质粒DNA的表达。随着水凝胶含水量的降低，基因表达的保留期延长。荧光显微镜研究显示，即使在植入7天后，植入的水凝胶周围也检测到质粒DNA- cg复合物，这与注射质粒DNA溶液有明显的对比。由此可见，在我们的水凝胶体系中，活性质粒DNA的释放伴随着水凝胶的体内降解，导致基因表达的延长。通过改变水凝胶的含水量，可以控制质粒DNA释放的时间分布和相应的基因表达。(C) 2002 Elsevier Science B.V.版权所有
This paper shows achievement of the in vivo controlled release of a plasmid DNA from a biodegradable hydrogel and the consequent regulation of gene expression period, Cationization of gelatin was preformed through introduction of ethylenediamine and the gelatin prepared was crosslinked by various concentrations of glutaraldehyde to obtain cationized gelatin (CG) hydrogels as the carrier of plasmid DNA. In vivo release of plasmid DNA from the CG hydrogels was compared with the in vivo degradation of hydrogels. When CG hydrogels incorporating I-125-labeled plasmid DNA were implanted into the femoral muscle of mice, the plasmid DNA radioactivity remaining decreased with time and the retention period prolonged with a decrease in the water content of hydrogels used. The higher the water content of I-125-labeled CG hydrogels, the faster the hydrogel radioactivity remaining decreased with time. The time profile of plasmid DNA remaining in the hydrogels was in good accordance with that of hydrogel radioactivity, irrespective of the water content. Intramuscular implantation of plasmid DNA-incorporated CG hydrogels enhanced significantly expression of the plasmid DNA around the implanted site. The retention period of gene expression became longer as the hydrogel water content decreased. Fluorescent microscopic study revealed that the plasmid DNA-CG complex was detected around the hydrogel implanted even after 7-day implantation in marked contrast to the injection of plasmid DNA solution. It was concluded that in our hydrogel system, active plasmid DNA was released accompanied with the in vivo degradation of hydrogel, resulting in extended gene expression. The time profile of plasmid DNA release and the consequent gene expression was controllable by changing the water content of hydrogels. (C) 2002 Elsevier Science B.V. All rights reserved.