Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation.
Regnier V, De Morre N, Jadoul A, Preat V
Universite Catholique de Louvain, Unite de Pharmacie Galenique, Avenue E. Mounier, 73, UCL 73.20, 1200 Brussels, Belgium.
Skin electroporation has great potential for topical delivery of oligonucleotides.
Controled therapeutic levels of an intact phosphorothioate oligonucleotide
(PS) can be reached in the viable tissue of the skin. The aim of this work
was to investigate the transport mechanisms of a PS in hairless rat skin
by electroporation, and hence to allow optimization of oligonucleotides
(ONs) topical delivery. The pulsing condition used was five exponentially-decaying
pulses of 100 V and 500 ms pulse time. The main mechanism of PS transport
in the skin viable tissues during pulsing was electrophoresis. The electroosmosis
contribution was negligible. Electrophoresis created within minutes a reservoir
of PS in the skin viable tissues, which persisted within a therapeutic
range of hours. A strong PS/stratum corneum interaction occurred.
Copyright 1998 Elsevier Science B.V.
PMID: 10387943, UI: 99317145