In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution

被引:185
作者
Gehl, J
Sorensen, TH
Nielsen, K
Raskmark, P
Nielsen, SL
Skovsgaard, T
Mir, LM
机构
[1] Univ Copenhagen, Herlev Hosp, Dept Oncol, DK-2730 Herlev, Denmark
[2] Univ Aalborg, Inst Elect Syst, Aalborg, Denmark
[3] Herlev Hosp, Dept Clin Physiol & Nucl Med, DK-2730 Herlev, Denmark
[4] Inst Gustave Roussy, Lab Physicochem & Pharmacol Biol Macromol, UMR 8532 CNRS, Villejuif, France
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 1999年 / 1428卷 / 2-3期
关键词
electroporation; electropermeabilization; E-field; 51-chromium-EDTA; muscle; mouse;
D O I
10.1016/S0304-4165(99)00094-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo electroporation is increasingly being used to deliver small molecules as well as DNA to tissues. The aim of this study was to quantitatively investigate in vivo electroporation of skeletal muscle, and to determine the threshold for permeabilization, We designed a quantitative method to study in vive electroporation, by measuring uptake of Cr-51-EDTA. As electrode configuration influences electric field (E-field) distribution, we developed a method to calculate this. Electroporation of mouse muscle tissue was investigated using either external plate electrodes or internal needle electrodes placed 4 mm apart, and eight pulses of 99 mu s duration at a frequency of 1 Hz. The applied voltage to electrode distance ratio was varied from 0 to 2.0 kV/cm. We found that: (1) the threshold for permeabilization of skeletal muscle tissue using short duration pulses was at an applied voltage to electrode distance ratio of 0.53 kV/cm (+/-0.03 kV/cm), corresponding to an E-field of 0.45 kV/cm; (2) there were two phases in the uptake of Cr-51-EDTA, the first indicating increasing permeabilization and the second indicating beginning irreversible membrane damage; and (3) the calculated E-field distribution was more homogeneous for plate than for needle electrodes, which was reflected in the experimental results. (C) 1999 Elsevier Science B.V. All rights reserved.
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页码:233 / 240
页数:8
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