Nitroxide delivery system for Nrf2 activation and skin protection

Maya Ben Yehuda Greenwald, Marina Frušić-Zlotkin, Yoram Soroka, Shmuel Ben Sasson, Havazelet Bianco-Peled, Ronit Bitton, Ron Kohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Abstract Cyclic nitroxides are a large group of compounds composed of diverse stable radicals also known as synthetic antioxidants. Although nitroxides are valuable for use in several skin conditions, in in vivo conditions they have several drawbacks, such as nonspecific dispersion in normal tissue, preferential renal clearance and rapid reduction of the nitroxide to the corresponding hydroxylamine. However, these drawbacks can be easily addressed by encapsulating the nitroxides within microemulsions. This approach would allow nitroxide activity and therefore their valuable effects (e.g. activation of the Keap1-Nrf2-EpRE pathway) to continue. In this work, nitroxides were encapsulated in a microemulsion composed of biocompatible ingredients. The nanometric size and shape of the vehicle microemulsion and nitroxide microemulsion displayed high similarity, indicating that the stability of the microemulsions was preserved. Our studies demonstrated that nitroxide microemulsions were more potent inducers of the Keap1-Nrf2-EpRE pathway than the free nitroxides, causing the activation of phase II enzymes. Moreover, microemulsions containing nitroxides significantly reduced UVB-induced cytotoxicity in the skin. Understanding the mechanism of this improved activity may expand the usage of many other Nrf2 modulating molecules in encapsulated form, as a skin protection strategy against oxidative stress-related conditions.

Original languageAmerican English
Article number11937
Pages (from-to)123-134
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
StatePublished - 31 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier B.V.


  • Microemulsion
  • Nitroxides
  • Nrf2
  • Oxidative stress
  • Phase II enzymes
  • Skin


Dive into the research topics of 'Nitroxide delivery system for Nrf2 activation and skin protection'. Together they form a unique fingerprint.

Cite this