Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Physicochemical, in vitro antioxidant and cytotoxic properties of water- soluble chitosan-lactose derivatives Joaquin Arata Badano a , Noelia Vanden Braber a , Yanina Rossi a , Ladislao Díaz Vergara a , Luciana Bohl a , Carina Porporatto a , R. Dario Falcone b , Mariana Montenegro a, ⁎ a Centro de Investigaciones y Transferencia de Villa María (CIT-VM), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Villa María (UNVM), Villa María, Argentina b Instituto para el Desarrollo Agroindustrial y de la Salud (IDAS), CONICET-UNRC, Departamento de Química, Universidad Nacional de Río Cuarto, Río Cuarto, Argentina ARTICLE INFO Keywords: Chitosan-lactose derivatives Maillard reaction Antioxidant activity Cytotoxicity ABSTRACT In this study, water-soluble chitosan (Ch) derivatives were synthesized by the Maillard reaction between Ch and lactose. The Ch derivatives were characterized by FT-IR, 1 H-NMR and SLS to determine their structure, degree of deacetylation (DD), and molecular weight (Mw). The solubility at physiological pH, the in vitro antioxidant activity against hydroxyl radical, anion superoxide radical and ABTS cation radical, and the cytotoxicity against epithelial cells of the rat ileum (IEC-18) were also evaluated. The Maillard reaction, derivatives with lower Mw and DD and greater solubility than Ch were obtained. The biological properties of the derivatives were de- pendent on the concentration, Mw and DD, with antioxidant activity greater than or equal to that of Ch and non- cytotoxic in a wide range of concentrations. The results indicate that Ch derivatization with lactose produces new water-soluble polysaccharides, with antioxidant activity and non-cytotoxic, which can be used as bioma- terials for food and pharmaceutical applications. 1. Introduction Chitosan (Ch) is a linear copolymer composed of randomly dis- tributed units of N-acetyl-D-glucosamine and D-glucosamine linked by β(1→4) bonds (Verlee, Mincke, & Stevens, 2017), obtained by partial deacetylation of chitin extracted from the exoskeleton of crustaceans, fungi and insects (Ying, Xiong, Wang, Sun, & Liu, 2011). It is bio- compatible, biodegradable and non-toxic, exhibits antioxidant, anti- bacterial and antifungal activities, and is used in agricultural, en- vironmental, food, and biomedical industries (Rao, Chawla, Chander, & Sharma, 2011; Verlee et al., 2017). However, Ch applications are lim- ited because of its poor solubility at neutral or basic pH, which has been attributed to the high crystallinity induced by hydrogen bonds and acetamido groups present in its structure (Sun, Shi, Wang, Fang, & Huang, 2017). Both the functional characteristics and drawbacks of Ch depend on its degree of deacetylation (DD), its molecular weight (Mw) and the distribution of acetyl groups along its main chain (Nguyen, Winnik, & Buschmann, 2009). Several studies have aimed at obtaining Ch derivatives with prop- erties different from or better than those of native Ch. Mourya and Inamdar (2008) reported many methods modify Ch, including qua- ternization, N-alkylation, hydroxylalkylation, carboxyalkylation, thiolation, and glycation, among others. The Maillard reaction (MR), which is also known as non-enzymatic browning reaction, is a reaction between nucleophilic amino groups (–NH 2 ) and carbonyl groups (–C = O) of reducing saccharides (Hodge, 1953). Due to its amino group, Ch can react by the MR with the carbonyl group of a reducing sugar. The MR consists of three main stages: the initial, intermediate and final stages. In the initial stage, the condensation between an amino group and a carbonyl group of reducing sugars forms a Schiff base which becomes an Amadori product via Amadori rearrangement. During this initial stage, the products formed are colorless. Throughout the intermediate stage, the reaction color becomes yellow with strong absorption in the near ultraviolet and may be detected by spectro- photometry at 294 nm. In the final stage, the compounds formed are highly colored and are detected at 420 nm (Gullón et al., 2016). Several works have reported that the MR products produced between Ch and mono- or disaccharides show promising antimicrobial and antioxidant activity, solubility and rheological characteristics (Gullón et al., 2016; Guo et al., 2015; Ying et al., 2011). It is known that the structure and physicochemical properties of polymers influence their biological properties (Aranaz et al., 2009). Most biological properties of Ch are related to its cationic character and to a lesser extent to its degree of polymerization, being the DD and Mw the parameters with the highest https://doi.org/10.1016/j.carbpol.2019.115158 Received 29 May 2019; Received in revised form 6 July 2019; Accepted 1 August 2019 ⁎ Corresponding author at: Universidad Nacional de Villa María, Av. Arturo Jauretche 1555, (5900), Villa María, Córdoba, Argentina. E-mail address: mamontenegro@conicet.gov.ar (M. Montenegro). Carbohydrate Polymers 224 (2019) 115158 Available online 08 August 2019 0144-8617/ © 2019 Elsevier Ltd. All rights reserved. T