Transscleral Iontophoretic Drug Delivery for Treating Retinal Diseases

  • Dherya Bahl
  • Rinda Devi Bachu
  • Mrudula Chitti
  • Pallabita Chowdhury
  • Jwala Renukuntla
  • Sai H. S. BodduEmail author


Drug delivery to the eye still is a challenge due to its intricate anatomical structure. Posterior segment delivery is much more challenging due to the acellular nature of the vitreous humor and the longer diffusion distance to the retina. Iontophoresis is a noninvasive technique that facilitates the movement of charged drug molecules into tissues by an electric field. Using iontophoresis, it is possible to achieve therapeutic concentrations faster by modulating the intensity and duration of the applied current. Transscleral iontophoretic delivery is gaining pace and is considered as an alternative for a safe and more effective treatment to retinal disorders. This chapter intends to highlight various aspects of iontophoresis, with a special emphasis on transscleral delivery of drugs and drug-loaded nanocarrier systems for treating disorders in the back of the eye. Finally, a section on toxic effects of iontophoresis to various ocular tissues is included.


Electrorepulsion Ions Current intensity Tissue barriers Ocular drug delivery Transscleral iontophoresis Posterior eye Retina 


  1. 1.
    Pal Kaur I, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002;28(5):473–93.CrossRefGoogle Scholar
  2. 2.
    HS Boddu S. Polymeric nanoparticles for ophthalmic drug delivery: an update on research and patenting activity. Recent Pat Nanomed. 2012;2(2):96–112.CrossRefGoogle Scholar
  3. 3.
    Ranta V-P, et al. Barrier analysis of periocular drug delivery to the posterior segment. J Control Release. 2010;148(1):42–8.PubMedCrossRefGoogle Scholar
  4. 4.
    HS Boddu S, Gupta H, Patel S. Drug delivery to the back of the eye following topical administration: an update on research and patenting activity. Recent Pat Drug Deliv Formul. 2014;8(1):27–36.CrossRefGoogle Scholar
  5. 5.
    Thompson JT. Cataract formation and other complications of intravitreal triamcinolone for macular edema. Am J Ophthalmol. 2006;141(4):629–37.PubMedCrossRefGoogle Scholar
  6. 6.
    Ozkiris A, Erkilic K. Complications of intravitreal injection of triamcinolone acetonide. Can J Ophthalmol. 2005;40(1):63–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Rhee DJ, et al. Intraocular pressure alterations following intravitreal triamcinolone acetonide. Br J Ophthalmol. 2006;90(8):999–1003.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Jonas JB. Intravitreal triamcinolone acetonide: a change in a paradigm. Ophthalmic Res. 2006;38(4):218–45.PubMedCrossRefGoogle Scholar
  9. 9.
    Sanborn GE, et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device. Arch Ophthalmol. 1992;110(2):188–95.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Janoria KG, et al. Novel approaches to retinal drug delivery. Expert Opin Drug Deliv. 2007;4(4):371–88.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Short BG. Safety evaluation of ocular drug delivery formulations: techniques and practical considerations. Toxicol Pathol. 2008;36(1):49–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Gaudana R, et al. Recent perspectives in ocular drug delivery. Pharm Res. 2009;26(5):1197–216.PubMedCrossRefGoogle Scholar
  13. 13.
    Russell R. Bioerodable eye implant may help treat macular edema. Pharm Technol. 2004;28(3):18.Google Scholar
  14. 14.
    Ambati J, et al. Transscleral delivery of bioactive protein to the choroid and retina. Invest Ophthalmol Vis Sci. 2000;41(5):1186–91.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Jiang J, et al. Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res. 2009;26(2):395–403.PubMedCrossRefGoogle Scholar
  16. 16.
    Bourges J-L, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest Ophthalmol Vis Sci. 2003;44(8):3562–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Patel S, et al. Development and evaluation of dexamethasone Nanomicelles with potential for treating posterior uveitis after topical application. J Ocul Pharmacol Ther. 2015;31(4):215–27.PubMedCrossRefGoogle Scholar
  18. 18.
    Vadlapudi AD, Mitra AK. Nanomicelles: an emerging platform for drug delivery to the eye. Ther Deliv. 2013;4(1):1.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Olsen TW, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142(5):777–87. e2PubMedCrossRefGoogle Scholar
  20. 20.
    Normand N, et al. VP22 light controlled delivery of oligonucleotides to ocular cells in vitro and in vivo. Mol Vis. 2005;11:184–91.PubMedGoogle Scholar
  21. 21.
    Eljarrat-Binstock E, Domb AJ. Iontophoresis: a non-invasive ocular drug delivery. J Control Release. 2006;110(3):479–89.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Thrimawithana TR, et al. Drug delivery to the posterior segment of the eye. Drug Discov Today. 2011;16(5):270–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Kompella UB, Kadam RS, Lee VH. Recent advances in ophthalmic drug delivery. Ther Deliv. 2010;1(3):435–56.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Molokhia SA, et al. Examination of barriers and barrier alteration in transscleral iontophoresis. J Pharm Sci. 2008;97(2):831–44.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Masada T, et al. Examination of iontophoretic transport of ionic drugs across skin: baseline studies with the four-electrode system. Int J Pharm. 1989;49(1):57–62.CrossRefGoogle Scholar
  26. 26.
    Srinivasan V, et al. Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery. J Pharm Sci. 1989;78(5):370–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Khan A, et al. Iontophoretic drug delivery: history and applications. J App Pharm Sci. 2011;1:11.Google Scholar
  28. 28.
    Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438–70.PubMedCrossRefGoogle Scholar
  29. 29.
    Leduc S. Introduction of medicinal substances into the depth of tissues by electric current. Ann Electrobiol. 1900;3:545–60.Google Scholar
  30. 30.
    Chien YW, Banga AK. Iontophoretic (transdermal) delivery of drugs: overview of historical development. J Pharm Sci. 1989;78(5):353–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Wirtz R. Die ionentherapie in der augenheilkunde. Klin Monatsbl Augenheilkd. 1908;46:543–79.Google Scholar
  32. 32.
    Karbowski M. Iontophoresis in ophthalmology (part 1 of 2). Ophthalmologica. 1939;97(3–4):166–83.CrossRefGoogle Scholar
  33. 33.
    Birkhauser R. Resultats d’etudes cliniques et experimentales sur la iontophorese. Rev Gen Ophtalmol. 1921;35:312–8.Google Scholar
  34. 34.
    Fietta P. Quelques essais d’iontophorese a l’atropine. Rev Gen Ophtalmol. 1924;38:317–28.Google Scholar
  35. 35.
    Morisot L. L'ionothérapie ou ionisation appliquée au traitement des affections oculaires. Clin Ophthalmol. 1927;31:5–16.Google Scholar
  36. 36.
    von Sallmann L. Sulfadiazine iontophoresis in pyocyaneus infection of rabbit cornea. Am J Ophthalmol. 1942;25(11):1292–300.CrossRefGoogle Scholar
  37. 37.
    Von Sallmann L. Further efforts to influence X-ray cataract by chemical agents. Trans Am Ophthalmol Soc. 1951;49:391.Google Scholar
  38. 38.
    Von Sallmann L. Experimental study on the vitreous: II. Experiments on disappearance of red blood cells from the vitreous. Arch Ophthalmol. 1950;43(4):638–52.CrossRefGoogle Scholar
  39. 39.
    von Sallmann L, Dillon B. Studies of the eye with radioiodine autographs. Am J Ophthalmol. 1950;33(3):429–40.CrossRefGoogle Scholar
  40. 40.
    von Sallmann L, et al. Study on penetration of cysteine and cystine into the aqueous humor of rabbits and its relation to early x-irradiation effects on the eye. Am J Ophthalmol. 1951;34(5):95–103.CrossRefGoogle Scholar
  41. 41.
    Maurice DM. Iontophoresis of fluorescein into the posterior segment of the rabbit eye. Ophthalmology. 1986;93(1):128–32.PubMedCrossRefGoogle Scholar
  42. 42.
    Barza M, Peckman C, Baum J. Transscleral iontophoresis of cefazolin, ticarcillin, and gentamicin in the rabbit. Ophthalmology. 1986;93(1):133–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Hughes L, Maurice DM. A fresh look at iontophoresis. Arch Ophthalmol. 1984;102(12):1825–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Behar-Cohen FF, et al. Ocular iontophoresis. In: Drug product development for the back of the eye: Springer, Boston, MA; 2011. p. 361–90.CrossRefGoogle Scholar
  45. 45.
    Bejjani RA, et al. Electrically assisted ocular gene therapy. Surv Ophthalmol. 2007;52(2):196–208.PubMedCrossRefGoogle Scholar
  46. 46.
    Li S, Hao J, Liddell M. Electrotransport across membranes in biological media: Electrokinetic theories and applications in drug delivery. In: Transport in biological media. Philadelphia: Elsevier; 2013. Ch 11.Google Scholar
  47. 47.
    Del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems: a shift to the posterior segment. Drug Discov Today. 2008;13(3):135–43.PubMedGoogle Scholar
  48. 48.
    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(2):315–29.PubMedCrossRefGoogle Scholar
  49. 49.
    Sarraf D, LEE DA. The role of iontophoresis in ocular drug delivery. J Ocul Pharmacol Ther. 1994;10(1):69–81.CrossRefGoogle Scholar
  50. 50.
    Behar-Cohen FF, et al. Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats. Exp Eye Res. 1997;65(4):533–45.PubMedCrossRefGoogle Scholar
  51. 51.
    Behar-Cohen F, et al. Transscleral coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels. Exp Eye Res. 2002;74(1):51–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Hayden BC, et al. Pharmacokinetics of systemic versus focal carboplatin chemotherapy in the rabbit eye: possible implication in the treatment of retinoblastoma. Invest Ophthalmol Vis Sci. 2004;45(10):3644–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Voigt M, et al. Ocular aspirin distribution: a comparison of intravenous, topical, and coulomb-controlled iontophoresis administration. Invest Ophthalmol Vis Sci. 2002;43(10):3299–306.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Dehghan M, Mouzam M. Advances in iontophoresis for drug delivery. Int J Health Res. 2008;1(3):115.Google Scholar
  55. 55.
    Halhal M, et al. Iontophoresis: from the lab to the bed side. Exp Eye Res. 2004;78(3):751–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Güngör S, et al. Trans-scleral iontophoretic delivery of low molecular weight therapeutics. J Control Release. 2010;147(2):225–31.PubMedCrossRefGoogle Scholar
  57. 57.
    Jones R, Maurice D. New methods of measuring the rate of aqueous flow in man with fluorescein. Exp Eye Res. 1966;5(3):208–20.PubMedCrossRefGoogle Scholar
  58. 58.
    Frucht-Pery J, et al. Iontophoresis–gentamicin delivery into the rabbit cornea, using a hydrogel delivery probe. Exp Eye Res. 2004;78(3):745–9.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Eljarrat-Binstock E, et al. Delivery of gentamicin to the rabbit eye by drug-loaded hydrogel iontophoresis. Invest Ophthalmol Vis Sci. 2004;45(8):2543–8.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Eljarrat-Binstock E, et al. Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel. J Control Release. 2005;106(3):386–90.PubMedCrossRefGoogle Scholar
  61. 61.
    Eljarrat-Binstock E, et al. Hydrogel probe for iontophoresis drug delivery to the eye. J Biomater Sci Polym Ed. 2004;15(4):397–413.PubMedCrossRefGoogle Scholar
  62. 62.
    Vollmer DL, et al. In vivo transscleral iontophoresis of amikacin to rabbit eyes. J Ocul Pharmacol Ther. 2002;18(6):549–58.PubMedCrossRefGoogle Scholar
  63. 63.
    Myles ME, Neumann DM, Hill JM. Recent progress in ocular drug delivery for posterior segment disease: emphasis on transscleral iontophoresis. Adv Drug Deliv Rev. 2005;57(14):2063–79.PubMedCrossRefGoogle Scholar
  64. 64.
    Hastings MS, et al. Visulex: advancing iontophoresis for effective noninvasive back-of-the-eye therapeutics. Drug Delivery Tech. 2004;4:53–7.Google Scholar
  65. 65.
    Pescina S, et al. Effect of formulation factors on the trans-scleral iontophoretic and post-iontophoretic transports of a 40kDa dextran in vitro. Eur J Pharm Sci. 2011;42(5):503–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Frucht-Pery J, et al. Iontophoretic treatment of experimental pseudomonas keratitis in rabbit eyes using gentamicin-loaded hydrogels. Cornea. 2006;25(10):1182–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Myles ME, Loutsch JM, Higaki S, Hill JM. Ocular iontophoresis: ophthalmic drug delivery systems. New York: Marcel Dekker; 2002.Google Scholar
  68. 68.
    Hill JM, O'Callaghan RJ, Hobden JA. Ocular iontophoresis: ophthalmic drug delivery systems. New York: Marcel Dekker; 1993.Google Scholar
  69. 69.
    Miller LL, Smith GA. Iontophoretic transport of acetate and carboxylate ions through hairless mouse skin. A cation exchange membrane model. Int J Pharm. 1989;49(1):15–22.CrossRefGoogle Scholar
  70. 70.
    Nicoli S, et al. Porcine sclera as a model of human sclera for in vitro transport experiments: histology, SEM, and comparative permeability. Mol Vis. 2009;15:259.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Berner B, Dinh SM. Electronically controlled drug delivery: CRC Press, Boca Raton, FL; 1998.Google Scholar
  72. 72.
    Green PG, et al. Lontophoretic delivery of amino acids and amino acid derivatives across the skin in vitro. Pharm Res. 1991;8(9):1113–20.PubMedCrossRefGoogle Scholar
  73. 73.
    Li SK, et al. Influence of asymmetric donor–receiver ion concentration upon transscleral iontophoretic transport. J Pharm Sci. 2005;94(4):847–60.PubMedCrossRefGoogle Scholar
  74. 74.
    Bockris JOM, Reddy AK. Modern electrochemistry 2B: electrodics in chemistry, engineering. In: Biology and environmental science, vol. 2: Springer Science & Business Media, Boston, MA; 2000.Google Scholar
  75. 75.
    Chopra P, Hao J, Li SK. Iontophoretic transport of charged macromolecules across human sclera. Int J Pharm. 2010;388(1):107–13.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Sung K, Fang J-Y, Hu OY-P. Delivery of nalbuphine and its prodrugs across skin by passive diffusion and iontophoresis. J Control Release. 2000;67(1):1–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Hayden B, et al. Iontophoretic delivery of carboplatin in a murine model of retinoblastoma. Invest Ophthalmol Vis Sci. 2006;47(9):3717–21.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Siddiqui O, et al. Facilitated transdermal transport of insulin. J Pharm Sci. 1987;76(4):341–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Phipps J, Padmanabhan R, Lattin G. Iontophoretic delivery model inorganic and drug ions. J Pharm Sci. 1989;78(5):365–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Rawat S, et al. Transdermal delivery by iontophoresis. Indian J Pharm Sci. 2008;70(1):5.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Molokhia S, et al. The influence of formulation factors on Transscleral Iontophoretic delivery of a macromolecule in vitro and in vivo. Invest Ophthalmol Vis Sci. 2013;54(15):3204.Google Scholar
  82. 82.
    Kirubakaran N, Chandrika M, Rani KRV. Iontophoresis: controlled transdermal drug delivery system. Int J Pharm Sci Res. 2015;6(8):3174.Google Scholar
  83. 83.
    Molokhia SA, et al. Examination of penetration routes and distribution of ionic permeants during and after transscleral iontophoresis with magnetic resonance imaging. Int J Pharm. 2007;335(1):46–53.PubMedCrossRefGoogle Scholar
  84. 84.
    Banga AK, Chien YW. Iontophoretic delivery of drugs: fundamentals, developments and biomedical applications. J Control Release. 1988;7(1):1–24.CrossRefGoogle Scholar
  85. 85.
    Abramowitz D, Neoussikine B. Treatment by ion transfer, vol. 87. New York: Grune and Stratton; 1946.Google Scholar
  86. 86.
    Lee TW-Y, Robinson JR. Drug delivery to the posterior segment of the eye II: development and validation of a simple pharmacokinetic model for subconjunctival injection. J Ocul Pharmacol Ther. 2004;20(1):43–53.PubMedCrossRefGoogle Scholar
  87. 87.
    Robinson MR, et al. A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide. Exp Eye Res. 2006;82(3):479–87.PubMedCrossRefGoogle Scholar
  88. 88.
    Li SK, Molokhia SA, Jeong E-K. Assessment of subconjunctival delivery with model ionic permeants and magnetic resonance imaging. Pharm Res. 2004;21(12):2175–84.PubMedCrossRefGoogle Scholar
  89. 89.
    Kim H, et al. Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging. Invest Ophthalmol Vis Sci. 2004;45(8):2722–31.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Li SK, Jeong E-K, Hastings MS. Magnetic resonance imaging study of current and ion delivery into the eye during transscleral and transcorneal iontophoresis. Invest Ophthalmol Vis Sci. 2004;45(4):1224–31.PubMedCrossRefGoogle Scholar
  91. 91.
    Molokhia SA, et al. Transscleral iontophoretic and intravitreal delivery of a macromolecule: study of ocular distribution in vivo and postmortem with MRI. Exp Eye Res. 2009;88(3):418–25.PubMedCrossRefGoogle Scholar
  92. 92.
    Holash JA, Stewart PA. The relationship of astrocyte-like cells to the vessels that contribute to the blood-ocular barriers. Brain Res. 1993;629(2):218–24.PubMedCrossRefGoogle Scholar
  93. 93.
    Barza M, Peckman C, Baum J. Transscleral iontophoresis as an adjunctive treatment for experimental endophthalmitis. Arch Ophthalmol. 1987;105(10):1418–20.PubMedCrossRefGoogle Scholar
  94. 94.
    CHOI TB, LEE DA. Transscleral and transcorneal iontophoresis of vancomycin in rabbit eyes. J Ocul Pharmacol Ther. 1988;4(2):153–64.CrossRefGoogle Scholar
  95. 95.
    YOSHIZUMI MO, et al. Experimental transscleral iontophoresis of ciprofloxacin. J Ocul Pharmacol Ther. 1991;7(2):163–7.CrossRefGoogle Scholar
  96. 96.
    Raiskup-Wolf F, et al. Delivery of gentamicin to the rabbit eye using hydrogel and iontophoresis. Ceska a slovenska oftalmologie: casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti. 2006;62(3):175–82.Google Scholar
  97. 97.
    Edelhauser HF, et al. Ophthalmic drug delivery systems for the treatment of retinal diseases: basic research to clinical applications. Invest Ophthalmol Vis Sci. 2010;51(11):5403–20.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Lam TT, et al. Transscleral iontophoresis of dexamethasone. Arch Ophthalmol. 1989;107(9):1368–71.PubMedCrossRefGoogle Scholar
  99. 99.
    Higuchi W, et al. Delivery of sustained release formulation of triamcinolone acetonide to the rabbit eye using the VisulexTM ocular iontophoresis device. Invest Ophthalmol Vis Sci. 2006;47(13):5108.Google Scholar
  100. 100.
    Eljarrat-Binstock E, et al. Methylprednisolone delivery to the back of the eye using hydrogel iontophoresis. J Ocul Pharmacol Ther. 2008;24(3):344–50.PubMedCrossRefGoogle Scholar
  101. 101.
    Kralinger MT, et al. Ocular delivery of acetylsalicylic acid by repetitive coulomb-controlled iontophoresis. Ophthalmic Res. 2003;35(2):102–10.PubMedCrossRefGoogle Scholar
  102. 102.
    Patane MA, et al. Evaluation of ocular and general safety following repeated dosing of dexamethasone phosphate delivered by transscleral iontophoresis in rabbits. J Ocul Pharmacol Ther. 2013;29(8):760–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Chopra P, Hao J, Li SK. Sustained release micellar carrier systems for iontophoretic transport of dexamethasone across human sclera. J Control Release. 2012;160(1):96–104.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Hayden BH, et al. Subconjunctival carboplatin in retinoblastoma: impact of tumor burden and dose schedule. Arch Ophthalmol. 2000;118(11):1549–54.PubMedCrossRefGoogle Scholar
  105. 105.
    Eljarrat–Binstock E, et al. Methotrexate delivery to the eye using transscleral hydrogel iontophoresis. Curr Eye Res. 2007;32(7–8):639–46.PubMedCrossRefGoogle Scholar
  106. 106.
    Lam TT, et al. Intravitreal delivery of ganciclovir in rabbits by transscleral iontophoresis. J Ocul Pharmacol Ther. 1994;10(3):571–5.CrossRefGoogle Scholar
  107. 107.
    Sarraf D, et al. Transscleral iontophoresis of foscarnet. Am J Ophthalmol. 1993;115(6):748–54.PubMedCrossRefGoogle Scholar
  108. 108.
    Yoshizumi MO, et al. Determination of ocular toxicity in multiple applications of foscarnet iontophoresis. J Ocul Pharmacol Ther. 1997;13(6):529–36.PubMedCrossRefGoogle Scholar
  109. 109.
    Asahara T, et al. Induction of gene into the rabbit eye by iontophoresis: preliminary report. Jpn J Ophthalmol. 2001;45(1):31–9.PubMedCrossRefGoogle Scholar
  110. 110.
    Voigt M, et al. Down-regulation of NOSII gene expression by iontophoresis of anti-sense oligonucleotide in endotoxin-induced uveitis. Biochem Biophys Res Commun. 2002;295(2):336–41.PubMedCrossRefGoogle Scholar
  111. 111.
    Pescina S, et al. In-vitro permeation of bevacizumab through human sclera: effect of iontophoresis application. J Pharm Pharmacol. 2010;62(9):1189–94.PubMedCrossRefGoogle Scholar
  112. 112.
    Tratta E, et al. In vitro permeability of a model protein across ocular tissues and effect of iontophoresis on the transscleral delivery. Eur J Pharm Biopharm. 2014;88(1):116–22.PubMedCrossRefGoogle Scholar
  113. 113.
    Chauvaud D, et al. Transscleral Iontophoresis of corticosteroids: phase II clinical trial. In: Investigative Ophthalmology & Visual Science. Rockville Pike: Assoc Research Vision Ophthalmology INC 9650; 2000.Google Scholar
  114. 114.
    Halhal M, et al. Corneal graft rejection and corticoid iontophoresis: 3 case reports. J Fr Ophtalmol. 2003;26(4):391–5.PubMedGoogle Scholar
  115. 115.
    Behar-Cohen F, et al. Reversal of corneal graft rejection by iontophoresis of methylprednisolone. Invest Ophthalmol Vis Sci. 2002;43(13):2214.Google Scholar
  116. 116.
    Parkinson T, et al. Tolerance of ocular iontophoresis in healthy volunteers. Invest Ophthalmol Vis Sci. 2002;43(13):1854.Google Scholar
  117. 117.
    Horwath-Winter J, et al. Iodide iontophoresis as a treatment for dry eye syndrome. Br J Ophthalmol. 2005;89(1):40–4.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Cohen A, et al. Clinical experience with the EyeGate® II delivery system (EGDS): safety and tolerability in healthy adult volunteers. Invest Ophthalmol Vis Sci. 2011;52(14):3224.Google Scholar
  119. 119.
    Domb AJ, Khan W. Focal controlled drug delivery: Springer Science & Business Media, Boston, MA; 2014.Google Scholar
  120. 120.
    Eljarrat-Binstock E, et al. Charged nanoparticles delivery to the eye using hydrogel iontophoresis. J Control Release. 2008;126(2):156–61.PubMedCrossRefGoogle Scholar
  121. 121.
    Wu C, Huang D, Wang L, Dong Y. A novel technology using transscleral iontophoresis to deliver protein drug-loaded nanoparticles to the posterior eye segment 2013; Available from:
  122. 122.
    Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv. 2014;11(3):393–407.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Yoshizumi MO, et al. Ocular toxicity of iontophoretic foscarnet in rabbits. J Ocul Pharmacol Ther. 1995;11(2):183–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Burnette RR, Marrero D. Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. J Pharm Sci. 1986;75(8):738–43.PubMedCrossRefGoogle Scholar
  125. 125.
    Barza M, Peckman C, Baum J. Transscleral iontophoresis of gentamicin in monkeys. Invest Ophthalmol Vis Sci. 1987;28(6):1033–6.PubMedGoogle Scholar
  126. 126.
    Lam TT, Fu J, Tso MO. A histopathologic study of retinal lesions inflicted by transscleral iontophoresis. Graefes Arch Clin Exp Ophthalmol. 1991;229(4):389–94.PubMedCrossRefGoogle Scholar
  127. 127.
    Grossman RE, Chu DF, Lee DA. Regional ocular gentamicin levels after transcorneal and transscleral iontophoresis. Invest Ophthalmol Vis Sci. 1990;31(5):909–16.PubMedGoogle Scholar
  128. 128.
    Gratieri T, Santer V, Kalia YN. Basic principles and current status of transcorneal and transscleral iontophoresis. Expert Opin Drug Deliv. 2017 Sep;14(9):1091–1102.PubMedCrossRefGoogle Scholar
  129. 129.
    Rajendra Vivek B. et al. Ocular iontophoresis: a review. Inventi impact: NDDS; 2010.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Dherya Bahl
    • 1
  • Rinda Devi Bachu
    • 1
  • Mrudula Chitti
    • 2
  • Pallabita Chowdhury
    • 1
  • Jwala Renukuntla
    • 2
  • Sai H. S. Boddu
    • 1
    Email author
  1. 1.College of Pharmacy and Pharmaceutical SciencesThe University of ToledoToledoUSA
  2. 2.Department of Pharmaceutical SciencesThe University of Texas at El Paso School of PharmacyEl PasoUSA

Personalised recommendations