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Electroporation-mediated delivery of 3'-protected phosphodiester oligodeoxynucleotides to the skin.
J Control Release. 2000 Jul 03; 67(2-3):337-46.JC

Abstract

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.

Authors+Show Affiliations

Université Catholique de Louvain, Unité de Pharmacie Galénique, Avenue E. Mounier, 73 UCL 73.20, 1200, Brussels, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10825565

Citation

Regnier, V, et al. "Electroporation-mediated Delivery of 3'-protected Phosphodiester Oligodeoxynucleotides to the Skin." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 67, no. 2-3, 2000, pp. 337-46.
Regnier V, Tahiri A, André N, et al. Electroporation-mediated delivery of 3'-protected phosphodiester oligodeoxynucleotides to the skin. J Control Release. 2000;67(2-3):337-46.
Regnier, V., Tahiri, A., André, N., Lemaître, M., Le Doan, T., & Préat, V. (2000). Electroporation-mediated delivery of 3'-protected phosphodiester oligodeoxynucleotides to the skin. Journal of Controlled Release : Official Journal of the Controlled Release Society, 67(2-3), 337-46.
Regnier V, et al. Electroporation-mediated Delivery of 3'-protected Phosphodiester Oligodeoxynucleotides to the Skin. J Control Release. 2000 Jul 3;67(2-3):337-46. PubMed PMID: 10825565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electroporation-mediated delivery of 3'-protected phosphodiester oligodeoxynucleotides to the skin. AU - Regnier,V, AU - Tahiri,A, AU - André,N, AU - Lemaître,M, AU - Le Doan,T, AU - Préat,V, PY - 2000/5/29/pubmed PY - 2000/9/19/medline PY - 2000/5/29/entrez SP - 337 EP - 46 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 67 IS - 2-3 N2 - 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. SN - 0168-3659 UR - https://www.unboundmedicine.com/medline/citation/10825565/Electroporation_mediated_delivery_of_3'_protected_phosphodiester_oligodeoxynucleotides_to_the_skin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168365900002236 DB - PRIME DP - Unbound Medicine ER -