1: Pharm Res 1998 Oct;15(10):1596-602
Localization of a FITC-labeled phosphorothioate oligodeoxynucleotide in
the skin after topical delivery by iontophoresis and electroporation.
Regnier V, Preat V
Universite Catholique de Louvain, Unite de Pharmacie Galenique, Brussels,
Belgium.
PURPOSE: The aim of this study was to verify the hypothesis that the application
of high voltage to the skin enhances both stratum corneum and keratinocyte
permeability. Therefore, the transport of FITC labelled phosphorothioate
oligonucleotides (FITC-PS) administered by passive diffusion, iontophoresis
or electroporation was localized. METHODS: Fluorescent microscopy and laser
scanning confocal microscopy were used to visualize the FITC-PS transport
at the tissue and cell level respectively in hairless rat skin after electroporation
(5 x (200 V approximately 500 ms) or iontophoresis (same amount of charges
transferred). RESULTS: FITC-PS did not penetrate the viable skin by passive
diffusion. Molecular transport in the skin upon electroporation or iontophoresis
was localized and implied mainly hair follicles for iontophoresis. In the
stratum corneum, the pathways for FITC-PS transport were more transcellular
during electroporation and paracellular during iontophoresis. FITC-PS were
detected in the nucleus of the keratinocytes a few minutes after pulsing.
In contrast, iontophoresis did not lead to an uptake of the oligomer.
CONCLUSIONS: The internalization of FITC-PS in the keratinocytes
after electroporation confirms the hypothesis and suggests that electroporation,
which allows both efficient topical delivery and rapid cellular uptake
of the oligonucleotides, might be useful for antisense therapy of epidermal
diseases.
PMID: 9794503, UI: 99008634