1: J Drug Target 1998;5(4):275-89
Parameters controlling topical delivery of oligonucleotides by electroporation.
Regnier V, Le Doan T, Preat V
Unite de Pharmacie Galenique, Universite Catholique de Louvain, Brussels,
Belgium.
Electroporation, using high voltage electrical pulses has been recognized
as a powerful method for delivering macromolecules such as DNA and proteins
in cells, or smaller molecules through the skin. Transdermal electroporation
could combine targeted delivery of drugs to the skin and permeabilization
of skin cells, suggesting that electroporation could be an interesting
alternative for topical delivery of oligonucleotides. This work is devoted
to the determination of the electroporation parameters that allow optimal
delivery of oligonucleotides to the viable tissues of hairless rat skin
in vitro. Phosphorothioate derivatives were preferred to the phosphodiester
congeners as the former were found to be much less degraded when extracted
from the tissues. Long duration (100-500 ms)--medium voltage (100-200 V)--exponentially
decaying pulses appeared to be the best conditions for delivering oligonucleotides
to the skin. The oligonucleotide quantity permeating the viable tissues
of the skin was controlled by the selection of the electrical parameters
of the pulses (voltage, pulse time and number of pulses) or by the ON concentration
in the donor compartment. After delivery by electroporation, therapeutic
levels of oligonucleotides were reached in the viable tissues of the skin
(above 1 microM or 10 microM in intact or stripped skin respectively).
Taken together, our results show that electroporation could be an interesting
method for the delivery of oligonucleotides to the skin.
PMID: 9713977, UI: 98377779