Iontophoresis Enhances Transdermal Delivery of Methylene Blue in Rat Skin (I): The Effect of Current Application Duration

  • Lee, Jae-Hyoung (Department of Physical Therapy, Electrotherapy Research Laboratory for Tissue Growth & Repair, Wonkwang Health Science University) ;
  • Choi, Eun-Young (Department of Physical Therapy, Kwangyang College)
  • Received : 2011.11.01
  • Accepted : 2011.11.25
  • Published : 2011.12.26

Abstract

Purpose: The objectives of this study were to determine the enhancing effect of iontophoresis method as it transdermally deliver methylene blue (MB) using visual examination, in terms of penetration depth and tissue distribution in the skin, and to determine the effect of application duration on the efficacy of iontophoresis. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into 5-, 10-, 20-, and 40-minute groups. These rats were exposed to either topical or anodic iontophoresis of 1% MB using a direct current of $0.5mA/cm^2$ for 5, 10, 20, and 40 minutes. Using cryosections of rat tissues, the penetration depth of MB was measured using light microscopy. Results: Significant differences in the penetration depth (F=54.20, p<0.001) were detected among the four groups. Post hoc comparisons of the penetration depth of MB data pooled across groups showed no significant difference between all topical application groups and 5-minute iontophoresis group, but did reveal a significant difference in the penetration depth between all topical application groups and 5-minute iontophoresis group versus 10-minute group, between the 10-minute and 20-minute group, and between the 20-minute and 40-minute iontophoresis group (p<0.05). Conclusion: The results demonstrate that iontophoresis enhances transdermal delivery of MB across stratum corneum of skin barrier by visual examination. Furthermore, the penetration depth of iontophoretic transdermal delivery of MB was dependent on the application duration. The duration of iontophoresis is one of the important factor in the efficacy of iontophoresis application.

Keywords

References

  1. Otberg N, Patzelt A, Rasulev U et al. The role of hair follicles in the percutaneous absorption of caffeine. Br J Clin Pharmacol. 2008;65(4):488-492. https://doi.org/10.1111/j.1365-2125.2007.03065.x
  2. Benson HA, Namjoshi S. Proteins and peptides: strategies for delivery to and across the skin. J Pharm Sci. 2008; 97(9):3591-3610. https://doi.org/10.1002/jps.21277
  3. Tanner T, Marks R. Delivering drugs by the transdermal route: review and comment. Skin Res Technol. 2008;14(3):249-260. https://doi.org/10.1111/j.1600-0846.2008.00316.x
  4. Groen D, Poole DS, Gooris GS, Bouwstra JA. Investigating the barrier function of skin lipid models with varying compositions. Eur J Pharm Biopharm. 2011;79(2):334-342. https://doi.org/10.1016/j.ejpb.2011.05.007
  5. Torin Huzil J, Sivaloganathan S, Kohandel M, Foldvari M. Drug delivery through the skin: molecular simulations of barrier lipids to design more effective noninvasive dermal and transdermal delivery systems for small molecules, biologics, and cosmetics. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3(5):449-462.
  6. Rao R, Nanda S. Sonophoresis: recent advancements and future trends. J Pharm Pharmacol. 2009;61(6):689-705. https://doi.org/10.1211/jpp.61.06.0001
  7. Rizwan M, Aqil M, Talegaonkar S, Azeem A, Sultana Y, Ali A. Enhanced transdermal drug delivery techniques: an extensive review of patents. Recent Pat Drug Deliv Formul. 2009; 3(2):105-124. https://doi.org/10.2174/187221109788452285
  8. Nanda A, Nanda S, Ghilzai NM. Current developments using emerging transdermal technologies in physical enhancement methods. Curr Drug Deliv. 2006;3(3):233-242. https://doi.org/10.2174/156720106777731091
  9. 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.
  10. Singh P, Roberts MS. Iontophoretic transdermal delivery of salicylic acid and lidocaine to local subcutaneous structures. J Pharm Sci. 1993;82(2):127-131. https://doi.org/10.1002/jps.2600820203
  11. Mathy FX, Lombry C, Verbeeck RK et al. Study of the percutaneous penetration of flurbiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat. J Pharm Sci. 2005;94(1):144-152. https://doi.org/10.1002/jps.20224
  12. Sintov AC, Brandys-Sitton R. Facilitated skin penetration of lidocaine: combination of a short-term iontophoresis and microemulsion formulation. Int J Pharm. 2006;316(1-2): 58-67. https://doi.org/10.1016/j.ijpharm.2006.02.034
  13. Glass JM, Stephen RL, Jacobson SC. The quantity and distribution of radiolabeled dexamethasone delivered to tissue by iontophoresis. Int J Dermatol. 1980;19(9):519-525. https://doi.org/10.1111/j.1365-4362.1980.tb00380.x
  14. Costello CT, Jeske AH. Iontophoresis: applications in transdermal medication delivery. Phys Ther. 1995;75(6): 554-563, 1995.
  15. Alvarez-Román R, Naik A, Kalia YN et al. Visualization of skin penetration using confocal laser scanning microscopy. Eur J Pharm Biopharm. 2004;58(2):301-316. https://doi.org/10.1016/j.ejpb.2004.03.027
  16. Fatouros DG, Groenink HW, de Graaff AM et al. Visualization studies of human skin in vitro/in vivo under the influence of an electrical field. Eur J Pharm Sci. 2006;29(2):160-170. https://doi.org/10.1016/j.ejps.2006.06.011
  17. Molokhia SA, Jeong EK, Higuchi WI 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(1-2):46-53. https://doi.org/10.1016/j.ijpharm.2006.11.001
  18. Riviere JE, Monteiro-Riviere NA, Inman AO. Determination of lidocaine concentrations in skin after transdermal iontophoresis: effects of vasoactive drugs. Pharm Res. 1992; 9(2):211-214. https://doi.org/10.1023/A:1018985323001
  19. Panus PC, Ferslew KE, Tober-Meyer B et al. Ketoprofen tissue permeation in swine following cathodic iontophoresis. Phys Ther. 1999;79(1):40-49.
  20. Bjerring P, Arendt-Nielsen L. Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream. Br J Anaesth. 1990;64(2):173-177. https://doi.org/10.1093/bja/64.2.173
  21. Ashburn MA, Gauthier M, Love G et al. Iontophoretic administration of 2% lidocaine HCl and 1:100,000 epinephrine in humans. Clin J Pain. 1997; 13(1):22-26. https://doi.org/10.1097/00002508-199703000-00005
  22. Johnson PG, Gallo SA, Hui SW et al. A pulsed electric field enhances cutaneous delivery of methylene blue in excised full-thickness porcine skin. J Invest Dermatol. 1998;111(3): 457-463. https://doi.org/10.1046/j.1523-1747.1998.00301.x
  23. Abla N, Naik A, Guy RH et al. Effect of charge and molecular weight on transdermal peptide delivery by iontophoresis. Pharm Res. 2005;22(12):2069-2078. https://doi.org/10.1007/s11095-005-8110-2
  24. Anderson CR, Morris RL, Boeh SD et al. Effects of iontophoresis current magnitude and duration on dexamethasone deposition and localized drug retention. Phys Ther. 2003;83(2):161-170.