Research Article Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System Maya Ben Yehuda Greenwald, 1,2,3,4 Marina Frušić-Zlotkin, 1 Yoram Soroka, 1 Shmuel Ben Sasson, 4 Ronit Bitton, 5,6 Havazelet Bianco-Peled, 2,3 and Ron Kohen 1 1 The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, 9112100 Jerusalem, Israel 2 Department of Chemical Engineering, Technion-Israel Institute of Technology, Technion City, 3200003 Haifa, Israel 3 The Russell Berrie Nanotechnology Institute and Technion-Israel Institute of Technology, 32000 Haifa, Israel 4 Department of Developmental Biology and Cancer Research, The Hebrew University Medical School, Ein-Karem Campus, 9112100 Jerusalem, Israel 5 Department of Chemical Engineering, Ben-Gurion University of the Negev, 8410501 Beer-Sheva, Israel 6 Ilse Katz Institute for Nanoscale Science and Technology, 8410501 Beer-Sheva, Israel Correspondence should be addressed to Ron Kohen; ronk@ekmd.huji.ac.il Received 24 October 2016; Revised 19 March 2017; Accepted 16 April 2017; Published 5 July 2017 Academic Editor: Luciano Saso Copyright © 2017 Maya Ben Yehuda Greenwald et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf 2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases. 1. Introduction The concept that antioxidants can protect cells and organs against oxidative stress has been established in numerous basic and clinical studies [1]. Nevertheless, nowadays, it has become evident that antioxidants of low molecular weight cannot protect the living organism against continuous stress and sometimes can even be deleterious [2]. Oxidants (electrophiles), on the other hand, were recently shown to be compounds capable of inducing cellular-protecting enzymes such as the phase II enzymes when provided in mod- erate concentrations. One of the basic factors activated when an electrophile is present is the transcription factor nuclear factor (erythroid-derived 2)-like 2, an NF-E2-related factor 2 (Nrf2), which is responsible for the induction of a variety of cytoprotective genes [3]. Regulated by the Keap1 metallopro- tein, Nrf2 is capable of inducing a large number of genes encoding antioxidant enzymes and genes enabling homeosta- sis and controlling processes involved in the pathology of many diseases (e.g., immune and inflammatory responses, tissue remodeling and fibrosis, carcinogenesis, and metastasis) [4, 5]. Nrf2 plays a vital and crucial role in the maintenance of skin homeostasis and repair and regeneration in various disease states of the skin [6]. However, acute and chronic Nrf2 activation in a healthy epidermis resulted in a negative effect on skin integrity [6]. Endogenous Nrf2 has the ability to protect skin against UV irradiation [6]. Nrf2 is also capable of decreasing symptoms of skin photoaging (e.g., wrinkle Hindawi Oxidative Medicine and Cellular Longevity Volume 2017, Article ID 5205471, 17 pages https://doi.org/10.1155/2017/5205471