Research Article Dual-Prevention for UV-Induced Skin Damage: Incorporation of Melatonin-Loaded Elastic Niosomes into Octyl Methoxycinnamate Pickering Emulsions Gulcin Arslan Azizoglu, 1 Sakine Tuncay Tanriverdi, 1 Fadime Aydin Kose, 2 Petek Ballar Kirmizibayrak, 2 and Ozgen Ozer 1,3 Received 17 February 2017; accepted 17 April 2017 Abstract. Incorporation of antioxidants into sunscreens is a logical approach, yet co-delivery of them with UV filters is a challenge. Here, we purposed a combination therapy, in which the chemical UV filter, octyl methoxycinnamate, was accumulated on upper skin while the antioxidant, melatonin, can penetrate deeper layers to show its effects. Melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion were prepared separately. Lyophilized elastic niosomes were dispersed into the Pickering emulsion to prepare the proposed combination formulation. The characterization studies of the formulations revealed that elastic niosomes can be prepared with tunable nanometer sizes, whereas Pickering emulsions can encapsulate the UV filter in micrometer-sized droplets. Melatonin-loaded elastic niosomes prepared with Tween80/Span80 mixture were 146 nm with a PI of 0.438, and 58.42% entrapment efficiency was achieved. The mean diameter size of the combination formulation was 27.8 μm. Ex vivo permeation studies revealed that 7.40% of octyl methoxycinnamate and 58% of melatonin were permeated through the rat skin while 27.6% octyl methoxycinnamate and 37% of melatonin accumulated in the skin after 24 h. Cell culture studies with real-time cell analyzer showed that the proposed formulation consist of melatonin-loaded elastic niosomes and octyl methoxycinnamate Pickering emulsion had no negative effect on the cell proliferation and viability. According to α,α-diphenyl-β- picrylhydrazyl free radical scavenging method, the proposed formulation showed as high antioxidant activity as melatonin itself. It is concluded that the proposed formulation would be a promising dual therapy for UV-induced skin damage with co-delivery strategy. KEY WORDS: elastic niosomes; Pickering emulsions; melatonin; octyl methoxycinnamate INTRODUCTION The incorporation of antioxidants into sunscreens has become a logical approach in order to scavenge free radicals generated by UV radiation that passes the outer layers of the skin (1–5). Therefore, co-delivery of an antioxidant and a UV filter is a challenge. In this study, we used octyl methoxycinnamate (OMC) as a UV filter and melatonin (MEL) as an antioxidant for dual targeting of UV-induced skin damage. Ultraviolet (UV) radiation is part of the electromagnetic spectrum emitted by the sun. Small amounts of UV are essential for health, but overexposure may result in acute and chronic health effects on the skin such as acute solar dermatitis, chronic photoaging, and even skin carcinogenesis. Oxidative stress is a known key factor for UV-mediated damaging events, represented by the generation of reac- tive oxygen species (ROS) or induction of oxidative DNA damage, which are also involved in skin aging and carcinogenesis (6). Sunscreens can help to protect skin from UV radiation in- duced damages. In fact, sunscreen usage is a necessity in our daily life especially for those parts of the body that remain exposed. Sunscreen products incorporate different chemicals that have high UV light absorbing properties, which are commonly referred to as UV filters. UV filters can be classified into two groups according to their nature. The inorganic UV filters, or also called physical UV filters, principally work by reflecting and scattering the UV radia- tion. However, a new study revealed that metal oxides like Electronic supplementary material The online version of this article (doi:10.1208/s12249-017-0786-1) contains supplementary material, which is available to authorized users. 1 Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Izmir, Turkey. 2 Department of Biochemistry, Faculty of Pharmacy, Ege University, Izmir, Turkey. 3 To whom correspondence should be addressed. (e-mail: ozgen.ozer@ege.edu.tr) AAPS PharmSciTech ( # 2017) DOI: 10.1208/s12249-017-0786-1 1530-9932/17/0000-0001/0 # 2017 American Association of Pharmaceutical Scientists