Therapeutic Applications of Electroporation

  • Muralikrishnan Angamuthu
  • S. Narasimha Murthy


Transdermal electroporation is an active drug permeation enhancement technique that produces transient aqueous pores in the intercellular lipid matrix of the stratum corneum. The electroporation protocols are efficiently tailored to achieve desired mass transfer into and across the skin, for therapeutic agents ranging from smaller molecules to macromolecules. The potential of transdermal electroporation has been demonstrated through the development of various treatment modalities in several preclinical and clinical studies. The ability of electroporation to administer macromolecules like insulin through the skin could be a potential alternative for subcutaneous injections. Electroporation was also shown to be useful in noninvasive transcutaneous sampling of drugs and diagnostic analytes. The design of electrodes was found to have significant influence on the skin permeabilization and tolerability of electrical protocol. More research needs to be undertaken to optimize the electroporation protocol, and electrode design before transdermal electroporation could be implemented in clinical practice.


Skin electroporation Fentanyl Insulin Co-enhancement techniques Microdialysis Noninvasive sampling Needle-type electrodes Intradermal vaccination Electrogene transfer and safety of needle-type electrodes 


  1. Babiuk S, Baca-Estrada M, Babiuk LA, Ewen C, Foldvari M (2000) Cutaneous vaccination: the skin as an immunologically active tissue and the challenge of antigen delivery. J Control Release 66(2–3):199–214CrossRefPubMedGoogle Scholar
  2. Bommannan DB, Tamada J, Leung L, Potts RO (1994) Effect of electroporation on transdermal iontophoretic delivery of luteinizing hormone releasing hormone (LHRH) in vitro. Pharm Res 11(12):1809–1814CrossRefPubMedGoogle Scholar
  3. Broderick KE, Shen X, Soderholm J, Lin F, McCoy J, Khan AS, Yan J, Morrow MP, Patel A, Kobinger GP, Kemmerrer S, Weiner DB, Sardesai NY (2011) Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device. Gene Ther 18(3):258–265CrossRefPubMedGoogle Scholar
  4. Byrne CM, Thompson JF, Johnston H, Hersey P, Quinn MJ, Michael Hughes T, McCarthy WH (2005) Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res 15(1):45–51CrossRefPubMedGoogle Scholar
  5. Chang SL, Hofmann GA, Zhang L, Deftos LJ, Banga AK (2000) The effect of electroporation on iontophoretic transdermal delivery of calcium regulating hormones. J Control Release 66(2–3):127–133CrossRefPubMedGoogle Scholar
  6. Denet AR, Preat V (2003) Transdermal delivery of timolol by electroporation through human skin. J Control Release 88(2):253–262CrossRefPubMedGoogle Scholar
  7. Dujardin N, Van Der Smissen P, Preat V (2001) Topical gene transfer into rat skin using electroporation. Pharm Res 18(1):61–66CrossRefPubMedGoogle Scholar
  8. Dujardin N, Staes E, Kalia Y, Clarys P, Guy R, Preat V (2002) In vivo assessment of skin electroporation using square wave pulses. J Control Release 79(1–3):219–227CrossRefPubMedGoogle Scholar
  9. Hallengard D, Haller BK, Maltais AK, Gelius E, Nihlmark K, Wahren B, Brave A (2011) Comparison of plasmid vaccine immunization schedules using intradermal in vivo electroporation. Clin Vaccine Immunol 18(9):1577–1581CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hao J, Li SK, Liu CY, Kao WW (2009) Electrically assisted delivery of macromolecules into the corneal epithelium. Exp Eye Res 89(6):934–941CrossRefPubMedPubMedCentralGoogle Scholar
  11. Jadoul A, Regnier V, Doucet J, Durand D, Preat V (1997) X-ray scattering analysis of human stratum corneum treated by high voltage pulses. Pharm Res 14(9):1275–1277CrossRefPubMedGoogle Scholar
  12. Jadoul A, Tanojo H, Preat V, Bouwstra JA, Spies F, Bodde HE (1998) Electroperturbation of human stratum corneum fine structure by high voltage pulses: a freeze-fracture electron microscopy and differential thermal analysis study. J Investig Dermatol Symp Proc 3(2):153–158CrossRefPubMedGoogle Scholar
  13. Jadoul A, Bouwstra J, Preat VV (1999) Effects of iontophoresis and electroporation on the stratum corneum. Review of the biophysical studies. Adv Drug Deliv Rev 35(1):89–105CrossRefPubMedGoogle Scholar
  14. Johansson DX, Ljungberg K, Kakoulidou M, Liljestrom P (2012) Intradermal electroporation of naked replicon RNA elicits strong immune responses. PLoS One 7(1):e29732CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kanitakis J (2002) Anatomy, histology and immunohistochemistry of normal human skin. Eur J Dermatol 12(4):390–399; quiz 400–1PubMedGoogle Scholar
  16. Lombry C, Dujardin N, Preat V (2000) Transdermal delivery of macromolecules using skin electroporation. Pharm Res 17(1):32–37CrossRefPubMedGoogle Scholar
  17. Murthy SN, Zhang S (2008) Electroporation and transcutaneous sampling (ETS) of acyclovir. J Dermatol Sci 49(3):249–251CrossRefPubMedGoogle Scholar
  18. Murthy SS, Kiran VS, Mathur SK, Murthy SN (2008) Noninvasive transcutaneous sampling of glucose by electroporation. J Diabetes Sci Technol 2(2):250–254CrossRefPubMedPubMedCentralGoogle Scholar
  19. Piggott JM, Sheahan BJ, Soden DM, O’Sullivan GC, Atkins GJ (2009) Electroporation of RNA stimulates immunity to an encoded reporter gene in mice. Mol Med Rep 2(5):753–756PubMedGoogle Scholar
  20. Pliquett U, Langer R, Weaver JC (1995) Changes in the passive electrical properties of human stratum corneum due to electroporation. Biochim Biophys Acta 1239(2):111–121CrossRefPubMedGoogle Scholar
  21. Prausnitz MR, Edelman ER, Gimm JA, Langer R, Weaver JC (1995) Transdermal delivery of heparin by skin electroporation. Biotechnology (N Y) 13(11):1205–1209Google Scholar
  22. Prommer E, Thompson L (2011) Intranasal fentanyl for pain control: current status with a focus on patient considerations. Patient Prefer Adherence 5:157–164CrossRefPubMedPubMedCentralGoogle Scholar
  23. Rabussay D (2008) Applicator and electrode design for in vivo DNA delivery by electroporation. Methods Mol Biol 423:35–59CrossRefPubMedGoogle Scholar
  24. Rastogi R, Anand S, Koul V (2010) Electroporation of polymeric nanoparticles: an alternative technique for transdermal delivery of insulin. Drug Dev Ind Pharm 36(11):1303–1311CrossRefPubMedGoogle Scholar
  25. Riviere JE, Monteiro-Riviere NA, Rogers RA, Bommannan D, Tamada JA, Potts RO (1995) Pulsatile transdermal delivery of LHRH using electroporation: drug delivery and skin toxicology. J Control Release 36(3):229–233CrossRefGoogle Scholar
  26. Roos AK, Moreno S, Leder C, Pavlenko M, King A, Pisa P (2006) Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol Ther 13(2):320–327CrossRefPubMedGoogle Scholar
  27. Roos AK, Eriksson F, Timmons JA, Gerhardt J, Nyman U, Gudmundsdotter L, Brave A, Wahren B, Pisa P (2009a) Skin electroporation: effects on transgene expression, DNA persistence and local tissue environment. PLoS One 4(9):e7226CrossRefPubMedPubMedCentralGoogle Scholar
  28. Roos AK, Eriksson F, Walters DC, Pisa P, King AD (2009b) Optimization of skin electroporation in mice to increase tolerability of DNA vaccine delivery to patients. Mol Ther 17(9):1637–1642CrossRefPubMedPubMedCentralGoogle Scholar
  29. Sen A, Daly ME, Hui SW (2002) Transdermal insulin delivery using lipid enhanced electroporation. Biochim Biophys Acta 1564(1):5–8CrossRefPubMedGoogle Scholar
  30. Vanbever R, Lecouturier N, Preat V (1994) Transdermal delivery of metoprolol by electroporation. Pharm Res 11(11):1657–1662CrossRefPubMedGoogle Scholar
  31. Vanbever R, Morre ND, Preat V (1996) Transdermal delivery of fentanyl by electroporation. II. Mechanisms involved in drug transport. Pharm Res 13(9):1360–1366CrossRefPubMedGoogle Scholar
  32. Vanbever R, Prausnitz MR, Preat V (1997) Macromolecules as novel transdermal transport enhancers for skin electroporation. Pharm Res 14(5):638–644CrossRefPubMedGoogle Scholar
  33. Vanbever R, Langers G, Montmayeur S, Preat V (1998a) Transdermal delivery of fentanyl: rapid onset of analgesia using skin electroporation. J Control Release 50(1–3):225–235CrossRefPubMedGoogle Scholar
  34. Vanbever R, Leroy MA, Preat V (1998b) Transdermal permeation of neutral molecules by skin electroporation. J Control Release 54(3):243–250CrossRefPubMedGoogle Scholar
  35. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, Leung L, Otten GR, Thudium K, Selby MJ, Ulmer JB (2000) Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 164(9):4635–4640CrossRefPubMedGoogle Scholar
  36. Wong TW, Chen CH, Huang CC, Lin CD, Hui SW (2006) Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery. J Control Release 110(3):557–565CrossRefPubMedGoogle Scholar
  37. Zewert TE, Pliquett UF, Vanbever R, Langer R, Weaver JC (1999) Creation of transdermal pathways for macromolecule transport by skin electroporation and a low toxicity, pathway-enlarging molecule. Bioelectrochem Bioenerg 49(1):11–20CrossRefPubMedGoogle Scholar
  38. Zupanic A, Kos B, Miklavcic D (2012) Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation. Phys Med Biol 57(17):5425–5440CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Muralikrishnan Angamuthu
    • 1
  • S. Narasimha Murthy
    • 2
  1. 1.Department of Pharmaceutics and Drug DeliveryThe University of MississippiOxfordUSA
  2. 2.Institute for Drug Delivery and Biomedical ResearchBangaloreIndia

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