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一种用于心脏基因治疗的无针液体喷射注射给药方法:与标准给药途径的比较评估显示治疗性保留增强且心脏特异性基因表达增加。

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

作者信息

Fargnoli A S, Katz M G, Williams R D, Margulies K B, Bridges Charles R

机构信息

Sanger Heart & Vascular Institute, Thoracic and Cardiac Surgery, Cannon Research Center, Carolinas Healthcare System, 1542 Garden Terrace, Charlotte, NC, 28203, USA.

出版信息

J Cardiovasc Transl Res. 2014 Nov;7(8):756-67. doi: 10.1007/s12265-014-9593-1. Epub 2014 Oct 15.

DOI:10.1007/s12265-014-9593-1
PMID:25315468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4261917/
Abstract

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 ± 4] % and LVIC-OCCL [58 ± 3] % groups p < 0.05 compared with IM [31 ± 8] % and LVIC [35 ± 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 ± 5] % and LVIC-OCCL [60 ± 8] % featuring more LV expression as compared with IM [30 ± 9] % and LVIC [23 ± 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

摘要

本研究评估了无针液体喷射法,并将其与三种常见的实验方法进行比较:(1)肌肉注射(IM),(2)左心室内输注(LVIC),以及(3)伴有主动脉和肺动脉闭塞的左心室内输注(LVIC - OCCL)。执行了两个方案。首先(n = 24只大鼠),在急性模型中,于给药后10分钟评估染料保留情况。急性研究结果如下:与IM组[31±8]%和LVIC组[35±4]%相比,液体喷射组[52±4]%和LVIC - OCCL组[58±3]%的左心室染料保留率(以心肌横截面积百分比表示)显著更高,p < 0.05。在第二个方案(n = 16只大鼠)中,每只动物接受单剂量编码绿色荧光蛋白的腺相关病毒(AAV.EGFP),终点为6周。在给予AAV.EGFP后6周的第二阶段,发现了类似的趋势,液体喷射组[54±5]%和LVIC - OCCL组[60±8]%在左心室中的表达高于IM组[30±9]%和LVIC组[23±9]%。IM组和LVIC - OCCL组的横截面显示有心肌纤维化。随着未来模型研究的更详细发展,无针液体喷射给药提供了一种改善直接心肌给药的有前景的策略。

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