Niosomes of Nerium oleander extracts: In vitro assessment of bioactive nanovesicular structures Aybike Gunes a , Emine Guler a, b , Rabia Nur Un c , Bilal Demir a , F. Baris Barlas c , Murat Yavuz a, d, * , Hakan Coskunol b , Suna Timur a, b, ** a Ege University, Faculty of Science, Department of Biochemistry, 35100 Bornova, Izmir, Turkey b Institute of Drug Abuse Toxicology & Pharmaceutical Sciences, Ege University, 35100 Bornova, Izmir, Turkey c Ege University, Faculty of Science, Department of Chemistry, 35100 Bornova, Izmir, Turkey d Dicle University, Faculty of Science, Department of Chemistry, 21280 Diyarbakir, Turkey article info Article history: Received 7 November 2016 Received in revised form 29 December 2016 Accepted 30 December 2016 Available online 30 December 2016 Keywords: Bioactive materials Drug carrier Nerium oleander Niosome Antioxidant activity Cytotoxicity abstract Niosomes are known as non-ionic surfactant-based vesicles and have been used quite a lot for medical applications as a novel drug delivery system in recent years. Herein we describe, the preparation and characterization of niosomes containing oleander (Nerium oleander) (ONs) extract as the herbal com- pound. In this context, niosomal formulations of two different extracts obtained from oleander roots were prepared by a thin film hydration technique using Tween 60 (non-ionic surfactant) with a cholesterol mixture at 1:1 M ratio. These vesicular structures were characterised by various techniques such as atomic force microscopy, zeta potential and dynamic light scattering size measurements. ONs vesicles are less than 100 nm in size with a good physical stability more than 50 days. Initially, total phenolic and flavonoid contents and antioxidant activities of the extracts were investigated. The methanol extract of oleander roots (MOE) showed higher polyphenolic content and exhibits a better antioxidant activity in compared to the hydro-methanol (20% methanol) extract (MOWE). Total phenolic contents in the MOE and MOWE were calculated as 64.51 ± 0.945 mg/mg and 65.05 ± 0.37 mg/mg gallic acid equivalents, respectively. Encapsulation efficiencies of the vesicles were found as 16.2% for MON (contain MOE) and 13.24% for MWON (contain MOWE). The significant linear correlation was confirmed between the antioxidant activity and total phenolic content of extracts as well as ONs. Cell based cytotoxic activities of methanol extract and MON formulations were also assessed via MTT assay using HeLa and A549 cell lines. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Nerium oleander , commonly known as oleander, is an orna- mental shrub or small plant that is a member of the Dogbane family (Apocynaceae), 2e6 m tall, widely cultivated in the Mediterranean region, subtropical Asia and many other warm regions [1e3]. It is grown outdoors in gardens and parks by people who may not consider its toxic potential [4,5]. Although all parts of oleander are toxic from roots to stems, from leaves to flowers and seeds owing to the oleandrigenin, oleandrin and other similar compounds, known as non-digitalis cardiac glycosides, it has many therapeutic uses in different traditional medicine all over the world [3,6e9]. The car- diac glycosides are well known for increasing cardiac contractility and have been traditionally used for treatment of congestive heart failure [10]. Oleander has been regarded as highly poisonous plant, which has been grown since ancient times, due to a number of its components that may show sign of toxicity. Oleander sap can cause severe eye inflammation, skin irritations and allergic reactions characterised by dermatitis [10e12]. All parts of the oleander plant contain cardiac glycosides, including stems, leaves, roots and even the smoke produced by burning, and they are poisonous to animals, human and certain insects [9,13,14]. Reactions to ingestion of this plant can include both cardiac and gastrointestinal effects. Although it is toxic to animals and human, oleander is proved to contain medicinal value like cardiotonic, diaphoretic, expectorant * Corresponding author. Department of Chemistry, Faculty of Science, Dicle University, 21280 Diyarbakir, Turkey. ** Corresponding author. Department of Biochemistry, Faculty of Science, Ege University, 35100 Bornova, Izmir, Turkey. E-mail addresses: myavuz@dicle.edu.tr (M. Yavuz), suna.timur@ege.edu.tr, sunatimur@yahoo.com (S. Timur). Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst http://dx.doi.org/10.1016/j.jddst.2016.12.013 1773-2247/© 2016 Elsevier B.V. All rights reserved. Journal of Drug Delivery Science and Technology 37 (2017) 158e165