J Control Release 2000 Jul 3;67(2-3):337-46

Electroporation-mediated delivery of 3'-protected phosphodiester 
oligodeoxynucleotides to the skin.


Regnier V, Tahiri A, Andre N, Lemaitre M, Le Doan T, Preat V

Universite Catholique de Louvain, Unite de Pharmacie Galenique, 
Avenue E. Mounier, 73 UCL 73.20, 1200, Brussels, Belgium.



The feasibility of topical delivery in the skin of 3' end modified
phosphodiester oligonucleotides using electroporation was investigated.
Experiments were performed in vitro, using hairless rat skin. Five pulses of
(200 V, 450 ms) were applied. The 3' end modifications of the 15 mer
oligonucleotide were: (1) 3'-aminohexyl, (2) biotin, with a triethyleneglycol
arm, (3) methylphosphonate links between nucleotides 13, 14 and 15, and (4)
2-O-methyl nucleotides at 13, 14 and 15 positions. All the modifications were
efficient to protect the oligonucleotides against degradation in the skin.
Electroporation increased the topical delivery of the 3' end-modified
phosphodiesters by two orders of magnitude compared to passive diffusion,
without significant differences between the derivatives. Oligonucleotide
concentrations in the range of 1 microm could be achieved in the viable skin.
The delivery of a phosphorothioate congener was lower than phosphodiester
delivery due to the interaction of phosphorothioate with the stratum corneum.
Consequently, 3' end-protected phosphodiesters could be an interesting
alternative to phosphorothioate oligonucleotides for topical treatment of
cutaneous diseases.


PMID: 10825565, UI: 20286708