Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation

Skin electroporation has great potential for topical delivery of oligonucle otides. Controlled therapeutic levels of an intact phosphorothioate oligonu cleotide (PS) can be reached in the viable tissue of the skin. The aim of t his work was to investigate the transport mechanisms of a PS in hairless ra t skin by electroporation, and hence to allow optimization of oligonucleoti des (ONs) topical delivery. The pulsing condition used was five exponential ly-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. T he electroosmosis contribution was negligible. Electrophoresis created with in minutes a reservoir of PS in the skin viable tissues, which persisted wi thin a therapeutic range for hours. A strong PS/stratum corneum interaction occured. (C) 1999 Elsevier Science B.V. All rights reserved.