Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation.

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.

In vivo noninvasive evaluation of hairless rat skin after high-voltage pulse exposure.

Short high-voltage pulses have recently been shown to dramatically increase and expedite transdermal drug transport via a mechanism hypothesized to involve electroporation. This study addresses tolerance issues of the method in vivo in hairless rat. Chromametry, transepidermal water loss (TEWL), laser Doppler flowmetry (LDF) and corneometry were jointly used for noninvasive sensing of skin biophysical parameters.

Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport.

Purpose: The aim of the present report was to systematically analyze the mechanisms involved in fentanyl transdermal transport by skin electroporation.

Methods: The study was performed in vitro with full-thickness hairless rat skin, skin electroporation being carried out with five exponentially-decaying pulses of 100 V applied voltage and around 600 ms pulse duration.

Results: Transport during and after pulsing are both important in transdermal delivery of fentanyl by skin electroporation.