Nitroxide delivery system for Nrf2 activation and skin protection

Area of Science:

• Biochemistry
• Dermatology
• Nanotechnology

Background:

• Cyclic nitroxides are stable radicals and synthetic antioxidants with therapeutic potential for skin conditions.
• In vivo, nitroxides face challenges like poor dispersion, rapid clearance, and reduction, limiting their efficacy.
• Microemulsion encapsulation offers a solution to overcome these limitations and enhance nitroxide delivery.

Purpose of the Study:

• To encapsulate cyclic nitroxides within biocompatible microemulsions.
• To evaluate the stability and efficacy of nitroxide-loaded microemulsions.
• To assess the impact of microencapsulation on nitroxide-mediated activation of the Keap1-Nrf2-EpRE pathway and skin protection.

Main Methods:

• Nitroxides were encapsulated in microemulsions using biocompatible ingredients.
• Physicochemical characterization of microemulsions and nitroxide-loaded microemulsions (size, shape).
• In vitro assessment of Keap1-Nrf2-EpRE pathway activation and UVB-induced cytotoxicity in skin models.

Main Results:

• Microemulsions and nitroxide-loaded microemulsions exhibited similar nanometric size and shape, confirming formulation stability.
• Nitroxide microemulsions demonstrated enhanced induction of the Keap1-Nrf2-EpRE pathway compared to free nitroxides.
• Microemulsions containing nitroxides significantly reduced UVB-induced skin cytotoxicity.

Conclusions:

• Microemulsion encapsulation improves the stability and potency of cyclic nitroxides for skin applications.
• This approach enhances the activation of the Keap1-Nrf2-EpRE pathway and provides protection against UVB-induced damage.
• Encapsulated Nrf2 modulators represent a promising strategy for managing oxidative stress-related skin conditions.