TRANSDERMAL TRANSPORT OF DNA ANTISENSE OLIGONUCLEOTIDES BY ELECTROPORATION

被引:80
作者
ZEWERT, TE [1 ]
PLIQUETT, UF [1 ]
LANGER, R [1 ]
WEAVER, JC [1 ]
机构
[1] HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139
关键词
D O I
10.1006/bbrc.1995.1968
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
Fluorescein-labeled antisense oligodeoxynucleotides (ODNs) corresponding to the promoters of the protooncogene c-myb (24-mer) and the oncogene c-myc (15-mer) were transported through the human skin in vitro by electroporation. Fluxes of 6.4+/-2.1 pM/cm(2)* hr and 11.5+/-3.5 pM/cm(2)* hr, respectively, were achieved during exponential pulsing [tau(pulse) = 1.1ms, transdermal voltage (U-skin)= 80V] every five seconds. The flux for U-skin <70V was undetectable, rapidly increased at 80V, but plateaued at higher values. Fluorescence imaging demonstrated that transport of the ODNs is concentrated in localized transport regions (LTRs)(1) approximately 30 mu m in diameter. (C) 1995 Academic Press, Inc.
引用
收藏
页码:286 / 292
页数:7
相关论文
共 22 条
[1]   OLIGODEOXYNUCLEOSIDE PHOSPHORAMIDATES AND PHOSPHOROTHIOATES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS [J].
AGRAWAL, S ;
GOODCHILD, J ;
CIVEIRA, MP ;
THORNTON, AH ;
SARIN, PS ;
ZAMECNIK, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (19) :7079-7083
[2]   IONTOPHORETIC DELIVERY OF DRUGS - FUNDAMENTALS, DEVELOPMENTS AND BIOMEDICAL APPLICATIONS [J].
BANGA, AK ;
CHIEN, YW .
JOURNAL OF CONTROLLED RELEASE, 1988, 7 (01) :1-24
[3]   ELECTROPORATION ENHANCES C-MYC ANTISENSE OLIGODEOXYNUCLEOTIDE EFFICACY [J].
BERGAN, R ;
CONNELL, Y ;
FAHMY, B ;
NECKERS, L .
NUCLEIC ACIDS RESEARCH, 1993, 21 (15) :3567-3573
[4]   NORMAL AND LEUKEMIC HEMATOPOIETIC-CELLS MANIFEST DIFFERENTIAL SENSITIVITY TO INHIBITORY EFFECTS OF C-MYB ANTISENSE OLIGODEOXYNUCLEOTIDES - AN INVITRO STUDY RELEVANT TO BONE-MARROW PURGING [J].
CALABRETTA, B ;
SIMS, RB ;
VALTIERI, M ;
CARACCIOLO, D ;
SZCZYLIK, C ;
VENTURELLI, D ;
RATAJCZAK, M ;
BERAN, M ;
GEWIRTZ, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) :2351-2355
[5]   IONTOPHORETIC (TRANSDERMAL) DELIVERY OF DRUGS - OVERVIEW OF HISTORICAL DEVELOPMENT [J].
CHIEN, YW ;
BANGA, AK .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1989, 78 (05) :353-354
[6]  
DASGUPTA P, 1989, ONCOGENE, V4, P1201
[7]   THEORY OF ELECTROPORATION OF PLANAR BILAYER-MEMBRANES - PREDICTIONS OF THE AQUEOUS AREA, CHANGE IN CAPACITANCE, AND PORE-PORE SEPARATION [J].
FREEMAN, SA ;
WANG, MA ;
WEAVER, JC .
BIOPHYSICAL JOURNAL, 1994, 67 (01) :42-56
[8]   OBSERVATION OF EXTREMELY HETEROGENEOUS ELECTROPORATIVE MOLECULAR UPTAKE BY SACCHAROMYCES-CEREVISIAE WHICH CHANGES WITH ELECTRIC-FIELD PULSE AMPLITUDE [J].
GIFT, EA ;
WEAVER, JC .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1995, 1234 (01) :52-62
[9]  
HADGRAFT J, 1989, DRUGS PHARM SCI
[10]  
HJIYA N, 1994, P NATL ACAD SCI USA, V91, P4499