Application of direct electric current to the corneal and conjunctival epithelia regulates the tight junctional assembly for ocular iontophoretic drug delivery

  • Hidehisa Sekijima Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan, https://orcid.org/0000-0001-6927-5625
  • Yutaro Hazama Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan, https://orcid.org/0000-0001-9444-0311
  • Soichiro Kimura Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan, https://orcid.org/0000-0003-1744-7397
  • Yasunori Morimoto Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan, https://orcid.org/0000-0001-8708-6908
  • Hideo Ueda Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan, https://orcid.org/0000-0002-0795-6262

Abstract

Objectives: In this study, we determined how iontophoresis (IP) affects tight junctions (TJs) in isolated rabbit corneas and conjunctiva.


Methods: Direct electric current in the range of 0.5–2.0 and 0.5–10 mA/cm2 were applied to the cornea and conjunctiva, respectively, for 30 min. The localization and expression levels of TJ-associated proteins were assessed before and after the application of the electric currents using immunostaining and western blotting.


Results: In both corneal and conjunctival epithelia, the localization of proteins, such as claudin-1, claudin-4, occludin, and ZO-1, was temporarily altered by anodal and cathodal IP; however, the protein relocalization was slower at higher currents. Additionally, in both anodal and cathodal IP, the expression levels of claudin-1 and occludin in the cornea and conjunctiva remained unchanged after the application of the electric currents compared with those before.


Conclusion: Our results indicated that the application of a direct electric current temporarily regulated TJ assemblies without altering the levels of TJ-associated proteins in both the cornea and conjunctiva. This temporary weakening of the paracellular barrier by the current may be responsible for the enhanced drug transport across the cornea and conjunctiva induced by ocular IP.


Keywords: ocular drug delivery, iontophoresis, electric current, cornea, conjunctiva, tight junction

Keywords: ocular drug delivery, iontophoresis, electric current, cornea, conjunctiva, tight junction

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Author Biographies

Hidehisa Sekijima, Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Department of Forensic Medicine and Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.

Yutaro Hazama, Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Soichiro Kimura, Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Yasunori Morimoto, Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Hideo Ueda, Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

Department of Hospital Pharmacy, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University; 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan,

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Sekijima H, Hazama Y, Kimura S, Morimoto Y, Ueda H. Application of direct electric current to the corneal and conjunctival epithelia regulates the tight junctional assembly for ocular iontophoretic drug delivery. JDDT [Internet]. 15Mar.2024 [cited 18Apr.2024];14(3):27-8. Available from: https://jddtonline.info/index.php/jddt/article/view/6455