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

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

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.

שפה מקוריתאנגלית
מספר המאמר11937
עמודים (מ-עד)123-134
מספר עמודים12
כתב עתEuropean Journal of Pharmaceutics and Biopharmaceutics
כרך94
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 31 מאי 2015

ASJC Scopus subject areas

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