Iontophoresis to Overcome the Challenge of Nail Permeation: Considerations and Optimizations for Successful Ungual Drug Delivery

AAPS J. 2021 Jan 13;23(1):25. doi: 10.1208/s12248-020-00552-y.


Iontophoresis is a widely used drug delivery technique that has been used clinically to improve permeation through the skin for drugs and other actives in topical formulations. It is however not commonly used for the treatment of nail diseases despite its potential to improve transungual nail delivery. Instead, treatments for nail diseases are limited to relatively ineffective topical passive permeation techniques, which often result in relapses of nail diseases due to the thickness and hardness of the nail barrier resulting in lower permeation of the actives. Oral systemic antifungal agents that are also used are often associated with various undesirable side effects resulting in low patient compliance. This review article discusses what is currently known about the field of transungual iontophoresis, providing evidence of its efficacy and practicality in delivering drug to the entire surface of the nail for extended treatment periods. It also includes relevant details about the nail structure, the mechanisms of iontophoresis, and the associated in vitro and in vivo studies which have been used to investigate the optimal characteristics for a transungual iontophoretic drug delivery system. Iontophoresis is undoubtedly a promising option to treat nail diseases, and the use of this technique for clinical use will likely improve patient outcomes.Graphical abstract.

Keywords: antifungal treatment; iontophoresis; nail psoriasis; onychomycosis; topical nail/transungual drug delivery.

Publication types

  • Review

MeSH terms

  • Administration, Topical
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Iontophoresis / methods*
  • Nail Diseases / drug therapy*
  • Nail Diseases / pathology
  • Nails / drug effects
  • Nails / metabolism*
  • Nails / pathology
  • Permeability
  • Treatment Outcome


  • Antifungal Agents