Localization of a FITC-labeled Phosphorothioate Oligodeoxynucleotide in the Skin After Topical Delivery by Iontophoresis and Electroporation

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 1998 Oct 30

PMID 9794503

Citations 8

Authors

V Regnier

V Preat

Affiliations

Soon will be listed here.

Abstract

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.

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References

Plenat F . Animal models of antisense oligonucleotides: lessons for use in humans. Mol Med Today. 1996; 2(6):250-7. DOI: 10.1016/1357-4310(96)88806-x. View

BELEHRADEK Jr J, Orlowski S, Ramirez L, Pron G, Poddevin B, Mir L . Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin. Biochim Biophys Acta. 1994; 1190(1):155-63. DOI: 10.1016/0005-2736(94)90045-0. View

Zhang L, Li L, Hoffmann G, Hoffman R . Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: an approach to gene therapy of skin aging and other diseases. Biochem Biophys Res Commun. 1996; 220(3):633-6. DOI: 10.1006/bbrc.1996.0455. View

Brand R, Iversen P . Iontophoretic delivery of a telomeric oligonucleotide. Pharm Res. 1996; 13(6):851-4. DOI: 10.1023/a:1016092809914. View

Regnier V, Le Doan T, Preat V . Parameters controlling topical delivery of oligonucleotides by electroporation. J Drug Target. 1998; 5(4):275-89. DOI: 10.3109/10611869808995881. View

Weaver J . Electroporation theory. Concepts and mechanisms. Methods Mol Biol. 1995; 47:1-26. DOI: 10.1385/0-89603-310-4:1. View

Crooke S, Bennett C . Progress in antisense oligonucleotide therapeutics. Annu Rev Pharmacol Toxicol. 1996; 36:107-29. DOI: 10.1146/annurev.pa.36.040196.000543. View

Zewert T, Pliquett U, Langer R, Weaver J . Transdermal transport of DNA antisense oligonucleotides by electroporation. Biochem Biophys Res Commun. 1995; 212(2):286-92. DOI: 10.1006/bbrc.1995.1968. View

Tonkinson J, Stein C . Antisense oligodeoxynucleotides as clinical therapeutic agents. Cancer Invest. 1996; 14(1):54-65. DOI: 10.3109/07357909609018436. View

10.

Noonberg S, Garovoy M, Hunt C . Characteristics of oligonucleotide uptake in human keratinocyte cultures. J Invest Dermatol. 1993; 101(5):727-31. DOI: 10.1111/1523-1747.ep12371683. View

11.

Prausnitz M, Gimm J, Guy R, Langer R, Weaver J, Cullander C . Imaging regions of transport across human stratum corneum during high-voltage and low-voltage exposures. J Pharm Sci. 1996; 85(12):1363-70. DOI: 10.1021/js960020s. View

12.

Vanbever R, LeBoulenge E, Preat V . Transdermal delivery of fentanyl by electroporation. I. Influence of electrical factors. Pharm Res. 1996; 13(4):559-65. DOI: 10.1023/a:1016093920875. View

13.

Graham M, Freier S, Crooke R, Ecker D, MASLOVA R, Lesnik E . Tritium labeling of antisense oligonucleotides by exchange with tritiated water. Nucleic Acids Res. 1993; 21(16):3737-43. PMC: 309879. DOI: 10.1093/nar/21.16.3737. View

14.

Regnier V, De Morre N, Jadoul A, Preat V . Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation. Int J Pharm. 1999; 184(2):147-56. DOI: 10.1016/s0378-5173(98)00085-4. View

15.

Monteiro-Riviere N, Inman A, Riviere J . Identification of the pathway of iontophoretic drug delivery: light and ultrastructural studies using mercuric chloride in pigs. Pharm Res. 1994; 11(2):251-6. DOI: 10.1023/a:1018907508501. View

16.

Giachetti C, Chin D . Increased oligonucleotide permeability in keratinocytes of artificial skin correlates with differentiation and altered membrane function. J Invest Dermatol. 1996; 106(3):412-8. DOI: 10.1111/1523-1747.ep12343419. View

17.

Titomirov A, Sukharev S, Kistanova E . In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim Biophys Acta. 1991; 1088(1):131-4. DOI: 10.1016/0167-4781(91)90162-f. View

18.

Chin D, Green G, Zon G, Szoka Jr F, Straubinger R . Rapid nuclear accumulation of injected oligodeoxyribonucleotides. New Biol. 1990; 2(12):1091-100. View

19.

Bergan R, Connell Y, Fahmy B, Neckers L . Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. Nucleic Acids Res. 1993; 21(15):3567-73. PMC: 331460. DOI: 10.1093/nar/21.15.3567. View

20.

Prausnitz M, Pliquett U, Langer R, Weaver J . Rapid temporal control of transdermal drug delivery by electroporation. Pharm Res. 1994; 11(12):1834-7. DOI: 10.1023/a:1018944223290. View