Skip to main content

Transdermal Delivery of Antisense Oligonucletoides

  • Protocol
Antisense Therapeutics

Part of the book series: Methods in Molecular Medicineā„¢ ((MIMM,volume 106))

  • 384 Accesses

Abstract

Transdermal delivery is an appealing method of introducing therapeutic agents because it allows medication to bypass the gastrointestinal (GI) tract. This reduces degradation by the acid and proteolytic enzymes in the gastric environment (1), as well hepatic first-pass elimination (2) and incomplete absorption due to GI motility disorders (3). Transdermal delivery also provides steady-state drug levels and improves patient compliance because of its extended duration. Another beneficial use of this technique is the treatment of skin disorders using local delivery of chemicals. Careful chemical design and formulation can modulate whether topically applied medications will reside within the skin or penetrate transdermally to achieve therapeutic systemic levels. The disadvantages of transdermal delivery include limited numbers of potential drug candidates due to their inability to penetrate the skin in sufficient levels, and potential irritation at the application site (4).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Guy, R. H. and Hadgraft, J. J. (1987) Transdermal drug delivery: a perspective. J. Control. Release 4, 237ā€“251.

    ArticleĀ  CASĀ  Google ScholarĀ 

  2. Pitt, C. G. (1990) The controlled parenteral delivery of polypeptides and proteins. Int. J. Pharm. 59, 173ā€“196.

    ArticleĀ  CASĀ  Google ScholarĀ 

  3. Brand, R. M. and Quigley, E. M. M. (1997) Transdermal delivery of erythromycin lactobionateā€”implications for the therapy of gastroparesis. Aliment. Pharmacol. Ther. 11, 589ā€“592.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  4. Hogan, D. J. and Cottan, J. (1996) Dermatological aspects of transdermal drug delivery systems, in Dermatotoxicology (Marzulli, F. N. and Maibaich, H. I., eds.), Taylor & Francis, Washington, DC, pp. 75ā€“86.

    Google ScholarĀ 

  5. Monteiro-Riviere, N. A. (1996) Anatomical factors affecting barrier function, in Dermatotoxicology (Marzulli, F. N. and Maibach, H. I., eds.), Taylor & Francis, Washington, DC, pp. 3ā€“19.

    Google ScholarĀ 

  6. Walters, K. A. (1989) Penetration enhancers and their use in transdermal therapeutic systems, in Transdermal Drug Delivery, (Hadgraft, J. and Guy, R. H., eds.), Marcel Dekker, New York, pp. 197ā€“247.

    Google ScholarĀ 

  7. Elias, P. M. (1983) Epidermal lipids, barrier function, and desquamation. J. Invest. Dermatol. 86, 187ā€“190.

    Google ScholarĀ 

  8. Wertz, P. W. and Downing, D. T. (1989) Stratum corneum: biological and biochemical considerations, in Transdermal Drug Delivery (Hadgraft, J. and Guy, R.H., eds.), Marcel Dekker, New York, pp. 1ā€“22.

    Google ScholarĀ 

  9. Junginger, H. E., Bodde, H. E., and de Haan, F. H. N. (1990) Visualization of drug transport across human skin and the influence of penetration enhancers, in Drug Permeation Enhancementā€“Theory and Applications (Hsieh, D. S., ed.) Marcel Dekker, Malvern, PA, pp. 59ā€“89.

    Google ScholarĀ 

  10. Cullander, C. and Guy, R. H. (1992) Routes of Delivery: case studies (6). Transdermal delivery of peptides and proteins. Adv. Drug Deliv. Rev. 8, 291ā€“329.

    ArticleĀ  CASĀ  Google ScholarĀ 

  11. Fartasch, M. (1996) The nature of the epidermal barrier: structural aspects. Adv. Drug Deliv. Rev. 18, 273ā€“282.

    ArticleĀ  CASĀ  Google ScholarĀ 

  12. Magee, F. P. (1996) Reaffirming the complexity of transdermal transport, in Dermatotoxicology (Marzulli, F. N. and Maibach, H. I., eds.), Taylor & Francis, Washington, DC, pp. 61ā€“74.

    Google ScholarĀ 

  13. Guy, R. H. and Hadgraft, J. (1989) Selection of drug candidates for transdermal drug delivery, in Transdermal Drug Delivery (Hadgraft, J. and Guy, R. H., eds.), Marcel Dekker, New York, pp. 59ā€“81.

    Google ScholarĀ 

  14. Tyle, P. (1986) Iontophoretic devices for drug delivery. Pharm. Res. 3, 318ā€“326.

    ArticleĀ  CASĀ  Google ScholarĀ 

  15. Singh, P. and Maibach, H. I. (1996) Iontophoresis: an alternative to the use of carriers in cutaneous drug delivery. Adv. Drug Deliv. Rev. 18, 379ā€“394.

    ArticleĀ  CASĀ  Google ScholarĀ 

  16. Ledger, P. W. (1992) Skin biological issues in electrically enhanced transdermal delivery. Adv. Drug Deliv. Rev. 9, 289ā€“307.

    ArticleĀ  CASĀ  Google ScholarĀ 

  17. Rosendal, T. (1942) Studies on the conducting properties of the humans skin to direct current. Acta. Physiol. Scand. 5, 130ā€“130.

    ArticleĀ  Google ScholarĀ 

  18. Kim, A., Green, P. G., Rao, G, and Guy, R. H. (1993) Convective solvent flow across the skin during iontophoresis. Pharm. Res. 10, 1315ā€“1320.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  19. Pikal, M. J. and Shah, S. (1990) Transport mechanisms in iontophoresis. III. An experimental study of the contributions of electroosmotic flow and permeability change in transport of low and high molecular weight solutes. Pharm. Res. 7, 222ā€“229.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  20. Brand, R. M. and Iversen, P. I. (1996) Iontophoretic delivery of a telomeric oligonucleotide. Pharm. Res. 13, 851ā€“854.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  21. Oldenburg, K. R., Vo, K. T., Smith, G A., and Selick, H. E. (1995) Iontophoretic delivery of oligonucleotides across full thickness hairless mouse skin. J. Pharm. Sci. 84, 915ā€“921.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  22. Brand, R. M., Wahl, A., and Iversen, P. L. (1997) Effects of size and sequence on the iontophoretic delivery of oligonucleotides. J. Pharm. Sci. 87, 49ā€“52.

    ArticleĀ  Google ScholarĀ 

  23. Brand, R. M., Hannah, T. L., Norris, J., and Iversen, P. L. (2001) Transdermal delivery of antisense oligonucleotides can induce changes in gene expression in vivo. Antisense Nucleic Acid Drug Dev. 11, 1ā€“6.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  24. Banga, A. K. and Prausnitz, M. R. (1998) Assessing the potential of skin electroporation for the delivery of protein-and gene-based drugs. TIBTECH 16, 408ā€“412.

    CASĀ  Google ScholarĀ 

  25. Banga, A. K., Bose, S., and Ghosh, T. K. (1999) Iontophoresis and electroporation: comparisons and contrasts. Int. J. Pharm. 179, 1ā€“19.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  26. Zewert, T. E., Pliquett, U. F., Langer, R., and Weaver, J. C. (1997) Transdermal transport of DNA amtosense oligonucleotides by electroporation. Biochem. Biophys. Res. Commun. 212, 286ā€“292.

    ArticleĀ  Google ScholarĀ 

  27. Regnier, V., Tahiri, A., Andre, N., Lemaitre, M., Le Doan, T., and Preat, V. (2000) Electroporation-mediated delivery of 3ā€²-protected phosphodiester oligodeoxynucleotides to the skin. J. Control Release 67, 337ā€“346.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  28. Regnier, V., LeDoan, T., and Preat, V. (1998) Parameters controlling topical delivery of oligonucleotides by electroporation. J. Drug Target 5, 275ā€“289.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  29. Regnier, V., De Morre, N., Jadoul, A., and Preat, V. (1999) Mechanisms of a phosphorothioate oligonucleotide delivery by skin electroporation. Int. J. Pharm. 184, 147ā€“156.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  30. McAllister, D. V., Allen, M. G., and Prausnitz, M. R. (2000) Microfabricated microneedles for gene and drug delivery. Ann. Rev. Biomed. Eng. 2, 289ā€“313.

    ArticleĀ  CASĀ  Google ScholarĀ 

  31. Lin, W., Cormier, M., Samiee, A., et al. (2001) Transdermal delivery of antisense oligonucleotides with microprojection patch (Macroflux) technology. Pharm. Res. 18, 1789ā€“1793.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  32. Hadgraft, J., Walters, K. A., and Guy, R. H. (1992) Epidermal lipids and topical drug delivery. Semin. Dermatol. 11, 139ā€“144.

    PubMedĀ  CASĀ  Google ScholarĀ 

  33. Yarosh, D. and Klein, J. (1996) The role of liposomal delivery incutaneous DNA repair. Adv. Drug Deliv. Rev. 18, 325ā€“333.

    ArticleĀ  CASĀ  Google ScholarĀ 

  34. Cevc, G., Blume, G., Schatzlein, A., Gebauer, D., and Paul, A. (1996) The skin: a pathway for systemic treatment with patches and lipid-based agent carriers. Adv. Drug Deliv. Rev. 18, 349ā€“378.

    ArticleĀ  CASĀ  Google ScholarĀ 

  35. Touitou, E., Dayan, N., Bergelson, L., Godin, B., and Eliaz, M. (2000) Ethosomesā€”novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J. Control Release 65, 403ā€“418.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  36. Mitragorti, S. (2000) Synergystic effect of enhancers for transdermal drug delivery. Pharm. Res. 17, 1354ā€“1359.

    ArticleĀ  Google ScholarĀ 

  37. Nolen III, H. W., Catz, P., and Friend, D. R. (1994) Percutaneous penetration of methyl phosphonate antisense oligonucleotides. Int. J. Pharm. 107, 169ā€“177.

    ArticleĀ  CASĀ  Google ScholarĀ 

  38. Pannier A. K., Arora, V., Iversen, P. L., and Brand, R. M. (2004) Transdermal delivery of phosphorodiamidate morpholino oligomers across hairless mouse skin. Int. J. Pharm. 275, 217ā€“226.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  39. Vlassov, V. V., Karamyshev, V. N., and Yakubov, L. A. (1993) Penetration of oligonucleotides into mouse organism through mucosa and skin. FEBS Lett. 327, 271ā€“274.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  40. Franz, T. J. (1975) Percutaneous absorption on the relevance of in vitro data. J. Invest. Dermatol. 64, 190ā€“195.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  41. Delgado-Charro, M. B. and Guy, R. H. (1995) Iontophoretic delivery of nafarelin across the skin. Int. J. Pharm. 117, 165ā€“172.

    ArticleĀ  CASĀ  Google ScholarĀ 

  42. Bronaugh, R. L. and Stewart, R. F. (1985) Methods for in vitro percutaneous absorption studies IV: the flow-through diffusion cell. J. Pharm. Sci. 74, 64ā€“67.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  43. Glikfeld, P., Cullander, C, Hinz, R. S., and Guy, R. H. (1998) A new system for in vitro studies of iontophoresis. Pharm. Res. 5, 443ā€“446.

    ArticleĀ  Google ScholarĀ 

  44. Bronaugh, R. L. (2000) In vitro percutaneous absorption models. Ann. NY Acad. Sci. 919, 188ā€“191.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  45. Mata, J. E., Jackson, J. D., Joshi, S. S., et al. (2000) Pharmacokinetics and in vivo effects of a six-base phosphorothioate oligodeoxynucleotide with anticancer and hematopoetic activites in swine. J. Hematother. Stem Cell Res. 9, 205ā€“214.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

  46. Gao, W. Y., Han, F. S., Storm, C., Egan, W., and Cheng, Y. C. (1992) Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology. Mol. Pharmacol. 41, 223ā€“229.

    PubMedĀ  CASĀ  Google ScholarĀ 

  47. Desjardins, J. P., Sproat, B. S., Beijer, B., et al. (1996) Pharmacokinetics of a synthetic, chemically modified hammerhead ribozyme against the rat cytochrome P-450 3A2 mRNA after single intravenous injections. J. Pharmacol. Exp. Ther. 278, 1419ā€“1427.

    PubMedĀ  CASĀ  Google ScholarĀ 

  48. Rowley, P. T., Kosciolek, B. A., and Kool, E. T. (1999) Circular antisense oligonucleotides inhibit growth of chronic myeloid leukemia cells. Mol. Med. 5, 693ā€“700.

    PubMedĀ  CASĀ  Google ScholarĀ 

  49. Iversen, P. L. (1902) Phosphorodiamidate morpholino oligomers: favorable properties for sequence-specific gene inactivation. Curr. Opin. Mol. Ther. 3, 235ā€“238.

    Google ScholarĀ 

  50. Freireich, E. J., Gehan, E. A., Rall, D. P., Schmidt, L. H., and Skipper, H. E. (1966) Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother. Rep. 50, 219ā€“244.

    PubMedĀ  CASĀ  Google ScholarĀ 

  51. Arora, V., Hannah, T. L., Iversen, P. L., and Brand, R. M. (2002) Transdermal use of phosphorodiamidate morpholino oligomer AVI-4472 inhibits cytochrome p450 3A2 activity in male rat. Pharm. Res. 19, 1465ā€“1470.

    ArticleĀ  PubMedĀ  CASĀ  Google ScholarĀ 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

Ā© 2005 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Brand, R.M., Iversen, P.L. (2005). Transdermal Delivery of Antisense Oligonucletoides. In: Phillips, M.I. (eds) Antisense Therapeutics. Methods in Molecular Medicineā„¢, vol 106. Humana Press. https://doi.org/10.1385/1-59259-854-4:255

Download citation

  • DOI: https://doi.org/10.1385/1-59259-854-4:255

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-205-6

  • Online ISBN: 978-1-59259-854-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics