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Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress

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Abstract

Transdermal drug delivery is limited by the stratum corneum of skin, which blocks most molecules, and thus, only few molecules with specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) are able to penetrate the skin. Recently, various technologies have been developed to overcome the strong barrier properties of stratum corneum. Iontophoresis technology, which uses a small current to improve drug permeation through skin, is one of the effective ways to circumvent the stratum corneum. This approach not only provides a more efficient, noninvasive, and patient-friendly method of drug delivery but also widens the scope of drugs for transdermal delivery. In this review, the mechanisms underlying iontophoresis and affecting factors are outlined. The focus will be on the latest advancements in iontophoretic transdermal drug delivery and application of iontophoresis with other enhancing technologies. The challenges of this technology for drug administration have also been highlighted, and some iontophoretic systems approved for clinical use are described.

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References

  1. Pastore MN, Kalia YN, Horstmann M, Roberts MS. Transdermal patches: history, development and pharmacology. Br J Pharmacol. 2015;172(9):2179–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lane ME. Skin penetration enhancers. Int J Pharm. 2013;447(1–2):12–21.

    Article  CAS  PubMed  Google Scholar 

  3. Ita K. Recent progress in transdermal sonophoresis. Pharm Dev Technol. 2017a;22(4):458–66.

    Article  CAS  PubMed  Google Scholar 

  4. Karande P, Mitragotri S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta. 2009;1788(11):2362–73.

    Article  CAS  PubMed  Google Scholar 

  5. Hadgraft J, Lane ME. Passive transdermal drug delivery systems. Am J Drug Deliv. 2006;4(3):153–60.

    Article  CAS  Google Scholar 

  6. Watkinson AC, Kearney MC, Quinn HL, Courtenay AJ, Donnelly RF. Future of the transdermal drug delivery market-have we barely touched the surface? Expert Opin Drug Deliv. 2016;13(4):523–32.

    Article  CAS  PubMed  Google Scholar 

  7. Thotakura N, Kaushik L, Kumar V, Preet S, Babu PV. Advanced approaches of bioactive peptide molecules and protein drug delivery systems. Curr Pharm Des. 2018;24(43):5147–63.

    Article  CAS  PubMed  Google Scholar 

  8. Dixit N, Bali V, Baboota S, Ahuja A, Ali J. Iontophoresis - an approach for controlled drug delivery: a review. Curr Drug Deliv. 2007;4(1):1–10.

    CAS  PubMed  Google Scholar 

  9. Ajay KB, Peter CP. lontophoretic devices: clinical applications and rehabilitation medicine. Crit Rev Phys Rehabil Med. 2017;29(1–4):247–79.

    Google Scholar 

  10. Ita K. Transdermal iontophoretic drug delivery: advances and challenges. J Drug Target. 2016;24(5):386–91.

    Article  CAS  PubMed  Google Scholar 

  11. Ita K. Percutaneous transport of psychotropic agents. J Drug Deliv Sci Technol. 2017b;39:247–59.

    Article  CAS  Google Scholar 

  12. Petrilli R, Lopez RFV. Physical methods for topical skin drug delivery: concepts and applications. Braz J Pharm Sci. 2018;54.

  13. Kalia YN, Naik A, Garrison J, Guy RH. Iontophoretic drug delivery. Adv Drug Deliv Rev. 2004;56:619–58.

    Article  CAS  PubMed  Google Scholar 

  14. Pikal MJ. The role of electroosmotic flow in transdermal iontophoresis. Adv Drug Deliv Rev. 2001;46(1–3):281–305.

    Article  CAS  PubMed  Google Scholar 

  15. Dhote V, Bhatnagar P, Mishra PK, Mahajan SC, Mishra DK. Iontophoresis: a potential emergence of a transdermal drug delivery system. Sci Pharm. 2012;80(1):1–28.

    Article  CAS  PubMed  Google Scholar 

  16. Manabe E, Numajiri S, Sugibayashi K, Morimoto Y. Analysis of skin permeation-enhancing mechanism of iontophoresis using hydrodynamic pore theory. J Control Release. 2000;66(2–3):149–58.

    Article  CAS  PubMed  Google Scholar 

  17. Arunkumar S, Ashok P, Desai BG, Shivakumar HN. Effect of chemical penetration enhancer on transdermal iontophoretic delivery of diclofenac sodium under constant voltage. J Drug Deliv Sci Technol. 2015;30:171–9.

    Article  CAS  Google Scholar 

  18. Djabri A, Guy RH, Delgado-Charro MB. Passive and iontophoretic transdermal delivery of phenobarbital: implications in paediatric therapy. Int J Pharm. 2012;435(1):76–82.

    Article  CAS  PubMed  Google Scholar 

  19. Kalaria DR, Singhal M, Patravale V, Merino V, Kalia YN. Simultaneous controlled iontophoretic delivery of pramipexole and rasagiline in vitro and in vivo: transdermal polypharmacy to treat Parkinson’s disease. Eur J Pharm Biopharm. 2018;127:204–12.

    Article  CAS  PubMed  Google Scholar 

  20. Gratieri T, Kalia YN. Mathematical models to describe iontophoretic transport in vitro and in vivo and the effect of current application on the skin barrier. Adv Drug Deliv Rev. 2013;65:315–29.

    Article  CAS  PubMed  Google Scholar 

  21. Cordery SF, Husbands SM, Bailey CP, Guy RH, Delgado-Charro MB. Simultaneous transdermal delivery of buprenorphine hydrochloride and naltrexone hydrochloride by iontophoresis. Mol Pharm. 2019;16(6):2808–16.

    Article  CAS  PubMed  Google Scholar 

  22. Patel N, Jain S, Lin S. Transdermal iontophoretic delivery of tacrine hydrochloride: correlation between in vitro permeation and in vivo performance in rats. Int J Pharm. 2016;513(1–2):393–403.

    Article  CAS  PubMed  Google Scholar 

  23. Djabri A, Guy RH, Delgado-Charro MB. Potential of iontophoresis as a drug delivery method for midazolam in pediatrics. Eur J Pharm Sci. 2019;128:137–43.

    Article  CAS  PubMed  Google Scholar 

  24. Ita KB, Banga AK. In vitro transdermal iontophoretic delivery of penbutolol sulfate. Drug Deliv. 2009;16(1):11–4.

    Article  CAS  PubMed  Google Scholar 

  25. Wang Y, Thakur R, Fan Q, Michniak B. Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery. Eur J Pharm Biopharm. 2005;60(2):179–91.

    Article  CAS  PubMed  Google Scholar 

  26. Ita K. Transcutaneous permeation of antiviral agents. J Drug Deliv Sci Technol. 2017c;41:293–302.

    Article  CAS  Google Scholar 

  27. Rac V, Levic S, Balanc B, Olalde Graells B, Bijelic G. PVA Cryogel as model hydrogel for iontophoretic transdermal drug delivery investigations. Comparison with PAA/PVA and PAA/PVP interpenetrating networks. Colloids Surf B Biointerfaces. 2019;180:441–8.

    Article  CAS  PubMed  Google Scholar 

  28. Ferreira JA, de Oliveira P, Pena G. Transdermal iontophoresis—a quantitative and qualitative study. Comput Math Appl. 2017;74(10):2231–42.

    Article  Google Scholar 

  29. Bashyal S, Lee S. Delivery of biopharmaceuticals using combination of liposome and iontophoresis: a review. J Pharm Invest. 2015;45(7):611–24.

    Article  CAS  Google Scholar 

  30. Subramony JA, Sharma A, Phipps JB. Microprocessor controlled transdermal drug delivery. Int J Pharm. 2006;317:1–6.

    Article  CAS  PubMed  Google Scholar 

  31. Marwah H, Garg T, Goyal AK, Rath G. Permeation enhancer strategies in transdermal drug delivery. Drug Deliv. 2016;23(2):564–78.

    Article  CAS  PubMed  Google Scholar 

  32. Del Río-Sancho S, Serna-Jimenez CE, Sebastian-Morello M, Calatayud-Pascual MA, Balaguer-Fernandez C, Femenia-Font A, Kalia YN, Merino V, Lopez-Castellano A. Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport. Int J Pharm. 2017;517(1–2):104–11.

    Article  PubMed  Google Scholar 

  33. Serna-Jiménez CE, del Rio SS, Calatayud-Pascual MA, Balaguer-Fernndez C, Femena-Font A, Lpez-Castellano A, Merino V. Development of antimigraine transdermal delivery systems of pizotifen malate. Int J Pharmaceut. 2015;492(1–2):223–32.

    Article  Google Scholar 

  34. Calatayud-Pascual MA, Sebastian-Morelló M, Balaguer-Fernández C, Delgado-Charro MB, López-Castellano A, Merino V. Influence of chemical enhancers and iontophoresis on the in vitro transdermal permeation of propranolol evaluation by dermatopharmacokinetics. Pharmaceutics. 2018;10(4).

  35. Puri A, Murnane KS, Blough BE, Banga AK. Effects of chemical and physical enhancement techniques on transdermal delivery of 3-fluoroamphetamine hydrochloride. Int J Pharm. 2017;528(1–2):452–62.

    Article  CAS  PubMed  Google Scholar 

  36. Arunkumar S, Shivakumar HN, Narasimha MS. Effect of terpenes on transdermal iontophoretic delivery of diclofenac potassium under constant voltage. Pharm Dev Technol. 2018;23(8):806–14.

    Article  CAS  PubMed  Google Scholar 

  37. Murari BM, Singh S, Manoharan M. Transdermal delivery of polidocanol from sol–gel patch: ex vivo skin permeation studies using iontophoresis for the treatment of varicose veins. J Sol-Gel Sci Technol. 2018;87(3):639–46.

    Article  CAS  Google Scholar 

  38. Nguyen HX, Banga AK. Electrically and ultrasonically enhanced transdermal delivery of methotrexate. Pharmaceutics. 2018;10(3):117.

    Article  CAS  PubMed Central  Google Scholar 

  39. Zuo J, Du L, Li M, Liu B, Zhu W, Jin Y. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs. Int J Pharm. 2014;466(1–2):76–82.

    Article  CAS  PubMed  Google Scholar 

  40. Kazemi M, Mombeiny R, Tavakol S, Keyhanvar P, Mousavizadeh K. A combination therapy of nanoethosomal piroxicam formulation along with iontophoresis as an anti-inflammatory transdermal delivery system for wound healing. Int Wound J. 2019;16(5):1144–52.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Liu S, Bao X, Zhang S, Zhang H, Lu X, Li T, Chen Z, Chen N. The study of ultrasound and iontophoresis on oxaprozin transdermal penetration using surface-enhanced Raman spectroscopy. Drug Deliv Transl Res. 2020;10:83–92.

    Article  CAS  PubMed  Google Scholar 

  42. Singhal M, Merino V, Rosini M, Cavalli A, Kalia YN. Controlled Iontophoretic delivery in vitro and in vivo of ARN14140— a multitarget compound for Alzheimer’s disease. Mol Pharm. 2019;16(8):3460–8.

    Article  CAS  PubMed  Google Scholar 

  43. Alvarez-Figueroa MJ, Delgado-Charro MB, Blanco-Mndez J. Passive and iontophoretic transdermal penetration of methotrexate. Int J Pharm. 2001;212(1):101–7.

    Article  CAS  PubMed  Google Scholar 

  44. Tfaili S, Gobinet C, Josse G, Angiboust JF, Manfait M, Piot O. Confocal Raman microspectroscopy for skin characterization: a comparative study between human skin and pig skin. Analyst. 2012;137(16):3673–82.

    Article  CAS  PubMed  Google Scholar 

  45. Takeuchi I, Suzuki T, Makino K. Skin permeability and transdermal delivery route of 50-nm indomethacin-loaded PLGA nanoparticles. Colloids Surf B Biointerfaces. 2017;159:312–7.

    Article  CAS  PubMed  Google Scholar 

  46. Cazares-Delgadillo J, Balaguer-Fernandez C, Calatayud-Pascual A, Ganem-Rondero A, Quintanar-Guerrero D, Lopez-Castellano AC, Merino V, Kalia YN. Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics. Eur J Pharm Biopharm. 2010;75(2):173–8.

    Article  CAS  PubMed  Google Scholar 

  47. Santos LF, Correia IJ, Silva AS, Mano JF. Biomaterials for drug delivery patches. Eur J Pharm Sci. 2018;118:49–66.

    Article  CAS  PubMed  Google Scholar 

  48. Talbi Y, Campo E, Brulin D, Fourniols JY. Controllable and re-usable patch for transdermal iontophoresis drug delivery. Electron Lett. 2018;54(12):739–40.

    Article  CAS  Google Scholar 

  49. Karjalainen E, Repasky GA. Molecular changes during acute myeloid leukemia (AML) evolution and identification of novel treatment strategies through molecular stratification. Prog Mol Biol Transl Sci. 2016;144:383–436.

    Article  CAS  PubMed  Google Scholar 

  50. Cazares-Delgadillo J, Ganem-Rondero A, Merino V, Kalia YN. Controlled transdermal iontophoresis for poly-pharmacotherapy: simultaneous delivery of granisetron, metoclopramide and dexamethasone sodium phosphate in vitro and in vivo. Eur J Pharm Sci. 2016;85:31–8.

    Article  CAS  PubMed  Google Scholar 

  51. Juluri A, Narasimha Murthy S. Transdermal iontophoretic delivery of a liquid lipophilic drug by complexation with an anionic cyclodextrin. J Control Release. 2014.

  52. Hegde AR, Rewatkar PV, Manikkath J, Tupally K, Parekh HS, Mutalik S. Peptide dendrimer-conjugates of ketoprofen: Synthesis and ex vivo and in vivo evaluations of passive diffusion, sonophoresis and iontophoresis for skin delivery. Eur J Pharm Sci. 2017;102:237–49.

    Article  CAS  PubMed  Google Scholar 

  53. Reis TA, Jaculi AE, Ramos KLV, Souza PEN, Veiga-Souza FH, Joanitti GA, Azevedo RB, Gratieri T, Cunha-Filho M, Gelfuso GM. Combination of cyclodextrin complexation and iontophoresis as a promising strategy for the cutaneous delivery of aluminum-chloride phthalocyanine in photodynamic therapy. Eur J Pharm Sci. 2019;139.

  54. Shiota K, Hama S, Yoshitomi T, Nagasaki Y, Kogure K. Prevention of UV-induced melanin production by accumulation of redox nanoparticles in the epidermal layer via iontophoresis. Biol Pharm Bull. 2017;40(6):941–4.

    Article  CAS  PubMed  Google Scholar 

  55. Park J, Lee H, Lim GS, Kim N, Kim D, Kim YC. Enhanced transdermal drug delivery by sonophoresis and simultaneous application of sonophoresis and iontophoresis. AAPS PharmSciTech. 2019;20(3).

  56. Bajracharya R, Song JG, Back SY, Han HK. Recent advancements in non-invasive formulations for protein drug delivery. Comput Struct Biotechnol J. 2019;17:1290–308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Pawar K, Kolli CS, Rangari VK, Babu RJ. Transdermal iontophoretic delivery of lysine-proline-valine (KPV) peptide across microporated human skin. J Pharm Sci. 2017;106(7):1814–20.

    Article  CAS  PubMed  Google Scholar 

  58. Yu T, Zhang S, Cao X, Liu C. Iontophoretic delivery of transdermal patches containing ropivacaine: sustaining the anesthetic effect in children. Acta Biochim Pol. 2019;66(2):167–72.

    CAS  PubMed  Google Scholar 

  59. Lee J, Kwon K, Kim M, Min J, Hwang NS, Kim WS. Transdermal iontophoresis patch with reverse electrodialysis. Drug Deliv. 2017;24(1):701–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kim KT, Lee J, Kim MH, Park JH, Lee JY, Song JH, Jung M, Jang MH, Cho HJ, Yoon IS, Kim DD. Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents. Drug Deliv. 2017;24(1):1204–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Noh G, Keum T, Seo JE, Bashyal S, Eum NS, Kweon MJ, Lee S, Sohn DH, Lee S. Iontophoretic transdermal delivery of human growth hormone (hGH) and the combination effect of a new type microneedle, Tappy Tok Tok®. Pharmaceutics. 2018;10(3):153.

    Article  CAS  PubMed Central  Google Scholar 

  62. Hashim IIA, Motoyama K, Abd-Elgawad AEH, El-Shabouri MH, Borg TM, Arima H. Potential use of iontophoresis for transdermal delivery of NF-kappaB decoy oligonucleotides. Int J Pharm. 2010;393(1–2):127–34.

    PubMed  Google Scholar 

  63. Ita K. Dermal/transdermal delivery of small interfering RNA and antisense oligonucleotides- advances and hurdles. Biomed Pharmacother. 2017d;87:311–20.

    Article  CAS  PubMed  Google Scholar 

  64. Tezel A, Dokka S, Kelly S, Hardee GE, Mitragotri S. Topical delivery of anti-sense oligonucleotides using low-frequency sonophoresis. Pharm Res. 2004;21:2219–25.

    Article  CAS  PubMed  Google Scholar 

  65. Tokumoto S, Higo N, Todo H, Sugibayashi K. Effect of combination of low-frequency sonophoresis or electroporation with iontophoresis on the mannitol flux or electroosmosis through excised skin. Biol Pharm Bull. 2016;39(7):1206–10.

    Article  CAS  PubMed  Google Scholar 

  66. Arunkumar S, Shivakumar HN, Desai BG, Ashok P. Effect of gel properties on transdermal iontophoretic delivery of diclofenac sodium. E-Polymers. 2016;16(1):25–32.

    Article  CAS  Google Scholar 

  67. Liu KC, Green CR, Alany RG, Rupenthal ID. Synergistic effect of chemical penetration enhancer and iontophoresis on transappendageal transport of oligodeoxynucleotides. Int J Pharm. 2013;441(1–2):687–92.

    Article  CAS  PubMed  Google Scholar 

  68. Munch S, Wohlrab J, Neubert RHH. Dermal and transdermal delivery of pharmaceutically relevant macromolecules. Eur J Pharm Biopharm. 2017;119:235–42.

    Article  CAS  PubMed  Google Scholar 

  69. Ronnander JP, Simon L, Koch A. Transdermal delivery of sumatriptan succinate using iontophoresis and dissolving microneedles. J Pharm Sci. 2019;108(11):3649–56.

    Article  CAS  PubMed  Google Scholar 

  70. Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol. 2008;26(11):1261–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Fatima T, Ajjarapu S, Shankar VK, Rangappa S, Shivakumar HN, Biswas SK, Hoque M, Murthy SN. Topical pilocarpine formulation for diagnosis of cystic fibrosis. J Pharm Sci. 2020;109(5):1747–51.

    Article  CAS  PubMed  Google Scholar 

  72. Dagash H, McCaffrey S, Mellor K, Roycroft A, Helbling I. Tap water iontophoresis in the treatment of pediatric hyperhidrosis. J Pediatr Surg. 2017;52(2):309–12.

    Article  PubMed  Google Scholar 

  73. Dogruk Kacar S, Ozuguz P, Eroglu S, Polat S, Karaca S. Treatment of primary hyperhidrosis with tap water iontophoresis in paediatric patients: a retrospective analysis. Cutan Ocul Toxicol. 2014;33(4):313–6.

    Article  CAS  PubMed  Google Scholar 

  74. Choi D-H, Thaxton A, Jeong IC, Kim K, Sosnay PR, Cutting GR, Searson PC. Sweat test for cystic fibrosis: wearable sweat sensor vs. standard laboratory test. J Cyst Fibros. 2018;17(4):e35–8.

    Article  PubMed  Google Scholar 

  75. Korsten MA, Lyons BL, Radulovic M, Cummings TM, Sikka G, Singh K, Hobson JC, Sabiev A, Spungen AM, Bauman WA. Delivery of neostigmine and glycopyrrolate by iontophoresis: a nonrandomized study in individuals with spinal cord injury. Spinal Cord. 2018;56(3):212–7.

    Article  PubMed  Google Scholar 

  76. Gaillard-Bigot F, Roustit M, Blaise S, Cracowski C, Seinturier C, Imbert B, Carpentier P, Cracowski JL. Treprostinil iontophoresis improves digital blood flow during local cooling in systemic sclerosis. Microcirculation. 2016;23(3):266–70.

    Article  CAS  PubMed  Google Scholar 

  77. Andanooru Chandrappa NK, Channakeshavaiah Ravikumar B, Rangegowda SM. Iontophoretic delivery of methotrexate in the treatment of palmar psoriasis: a randomised controlled study. Australas J Dermatol. 2020.

  78. Jijie R, Barras A, Boukherroub R, Szunerits S. Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures. J Mater Chem B. 2017;5(44):8653–75.

    Article  CAS  PubMed  Google Scholar 

  79. Zhang Y, Yu J, Kahkoska AR, Wang J, Buse JB, Gu Z. Advances in transdermal insulin delivery. Adv Drug Deliv Rev. 2019;139:51–70.

    Article  CAS  PubMed  Google Scholar 

  80. Dubey S, Kalia YN. Electrically-assisted delivery of an anionic protein across intact skin: cathodal iontophoresis of biologically active ribonuclease T1. J Control Release. 2011;152(3):356-362.

  81. Merino V, Kalia YN, Guy RH. Transdermal therapy and diagnosis by iontophoresis. Trends Biotechnol. 1997;15(8):288–90.

    Article  CAS  PubMed  Google Scholar 

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This work was supported by the National Natural Science Foundation of China (No: 81703452) and Double first-class innovative team (CPU2018GY28).

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  1. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Jiangsu Province, Nanjing, 211198, China

    Yu Wang, Lijuan Zeng, Wenting Song & Jianping Liu

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  1. Yu Wang
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Wang, Y., Zeng, L., Song, W. et al. Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress. Drug Deliv. and Transl. Res. 12, 15–26 (2022). https://doi.org/10.1007/s13346-021-00898-6

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