IONTOPHORETIC DELIVERY OF OLIGONUCLEOTIDES ACROSS FULL-THICKNESS HAIRLESS MOUSE SKIN

被引:49
作者
OLDENBURG, KR
VO, KT
SMITH, GA
SELICK, HE
机构
[1] Affymax Research Institute, Palo Alto, California, 94304
关键词
D O I
10.1002/jps.2600840803
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In recent years there has been an increased interest in the use of oligonucleotides as therapeutic agents. Oligonucleotide therapeutics may have significant potential over traditional drugs due to their high degree of specificity and increased affinity. The major drawbacks to the use of oligonucleotide therapeutics are the problems associated with their delivery and their relative instability in serum. The serum instability problem has been partially overcome through the use of oligonucleotides with modified backbones. Transdermal electrotransport may be used to overcome the problems associated with delivery. Here we report the use of transdermal electrotransport in the delivery of oligonucleotides across hairless mouse skin. The effects of pH, salt concentration, current density, and oligonucleotide concentration, structure, and length have been investigated.
引用
收藏
页码:915 / 921
页数:7
相关论文
共 32 条
[21]   TRANSPORT MECHANISMS IN IONTOPHORESIS .2. ELECTROOSMOTIC FLOW AND TRANSFERENCE NUMBER MEASUREMENTS FOR HAIRLESS MOUSE SKIN [J].
PIKAL, MJ ;
SHAH, S .
PHARMACEUTICAL RESEARCH, 1990, 7 (03) :213-221
[22]   TRANSPORT MECHANISMS IN IONTOPHORESIS .1. A THEORETICAL-MODEL FOR THE EFFECT OF ELECTROOSMOTIC FLOW ON FLUX ENHANCEMENT IN TRANSDERMAL IONTOPHORESIS [J].
PIKAL, MJ .
PHARMACEUTICAL RESEARCH, 1990, 7 (02) :118-126
[23]  
Rein H, 1926, Z BIOL-MUNICH, V85, P217
[24]  
ROSENDAL T, 1942, ACTA PHYSL SCAND, V5, P130
[25]  
Sambrook J., 1989, MOL CLONING LAB MANU
[26]   MECHANISM OF PERCUTANEOUS ABSORPTION .4. PENETRATION OF NONELECTROLYTES (ALCOHOLS) FROM AQUEOUS-SOLUTIONS AND FROM PURE LIQUIDS [J].
SCHEUPLEIN, RJ ;
BLANK, IH .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1973, 60 (05) :286-296
[27]   RANDOM BRICK MODEL FOR DRUG TRANSPORT ACROSS STRATUM-CORNEUM [J].
TOJO, K .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1987, 76 (12) :889-891
[28]   PERMEABILITY OF MAMMALIAN SKIN TO IONS [J].
TREGEAR, RT .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1966, 46 (01) :16-&
[29]   A DNA APTAMER WHICH BINDS TO AND INHIBITS THROMBIN EXHIBITS A NEW STRUCTURAL MOTIF FOR DNA [J].
WANG, KY ;
MCCURDY, S ;
SHEA, RG ;
SWAMINATHAN, S ;
BOLTON, PH .
BIOCHEMISTRY, 1993, 32 (08) :1899-1904
[30]  
WEDER HJ, 1969, J MEMBRANE BIOL, V1, P92