Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Diethyldithiocarbamate loaded in beeswax-copaiba oil nanoparticles obtained by solventless double emulsion technique promote promastigote death in vitro Karin Luize Mazur a , Paulo Emílio Feuser a , Alexsandra Valério a , Arthur Poester Cordeiro a , Camila Indiani de Oliveira b , João Paulo Assolini c , Wander Rogério Pavanelli c , Claudia Sayer a , Pedro H. H. Araújo a, ⁎ a Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Brazil b Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil c Laboratory of Experimental Protozoology, Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, PR, Brazil ARTICLE INFO Keywords: Solid lipid nanoparticles Diethyldithiocarbamate Hydrophilic drugs Beeswax L. amazonensis ABSTRACT Leishmaniasis is considered a neglected tropical disease that represents a Public Health problem due to its high incidence. In the search of new alternatives for Leishmaniasis treatment diethyldithiocarbamate (DETC) has shown an excellent leishmanicidal activity and the incorporation into drug carrier systems, such as solid lipid nanoparticles (SLNs), is very promising. In the present work DETC loaded in beeswax nanoparticles containing copaiba oil were obtained by the double emulsion/melt technique. The nanoparticles were characterized and leishmanicidal activity against L. amazonensis promastigotes forms and cytotoxicity in murine macrophages were evaluated. SLNs presented size below 200 nm, spherical morphology, negative charge surface, high encapsula- tion efficiency, above 80%, and excellent stability. Moreover, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses were performed to evaluate the chemical structure and possible interactions between DETC and SLNs. SLNs provided a protection for DETC, decreasing its cytotoxic effects in macrophages, which led to an improvement in the selectivity against the parasites, which almost doubled from free DETC (11.4) to DETC incorporated in SLNs (18.2). These results demonstrated that SLNs had a direct effect on L. amazonensis promastigotes without affect the viability of macrophage cell, can be a promising alternative therapy for the cutaneous treatment of L. amazonensis 1. Introduction American Cutaneous Leishmaniasis (ACL) is caused by protozoa of the genus Leishmania and is recognized by the World Health Organization (WHO) as a neglected tropical disease. This disease pre- sents manifestations ranging from the formation of the single ulcer to disseminated forms and can affect the mucous [1,2]. It consists of a Public Health problem, due to its high incidence, wide distribution and great complexity, with the possibility of the appearance of destructive, disfiguring and even incapacitating lesions for infected individuals [3,4]. Despite advances in parasite studies, as well as knowledge of the disease, therapies have now been based on the use of pentavalent an- timonials such as sodium stibogluconate (Pentostam®) and antimoniate N-methyl-glucamine (Glucantime®), besides the use of amphotericin B or pentamidines, however they present difficulties of administration, high cost and important side effects [5–7]. In search of new alternatives for Leishmaniasis treatment the Diethyldithiocarbamate (DETC) has shown an excellent leishmanicidal activity, being promising as new antileishmanicidal drug [8–10]. DETC a hydrophilic compound, is a member of the dithiocarbamate family and a potent metal-chelating agent with a dithiocarboxy functional group conjugated to an aliphatic secondary amino group [11,12]. Ac- cording to Celes et al. (2016), the use of DETC-based bacterial cellulose bio-curatives, a copper chelating agent that targets SOD1, significantly reduces Leishmania brasiliensis infection in vitro and in vivo, due to the increased superoxide levels [8]. The development of new drug-delivery systems to treat leishma- niasis, such as solid lipid nanoparticles (SLNs), represent an excellent alternative for leishmaniasis treatment [7,13]. SLNs have been reported as an efficient drug delivery system due to various advantages such as https://doi.org/10.1016/j.colsurfb.2018.12.048 Received 20 September 2018; Received in revised form 28 November 2018; Accepted 18 December 2018 ⁎ Corresponding author at: Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, 88010 970, Florianopolis, SC, Brazil. E-mail address: pedro.h.araujo@ufsc.br (P.H.H. Araújo). Colloids and Surfaces B: Biointerfaces 176 (2019) 507–512 Available online 18 December 2018 0927-7765/ © 2018 Elsevier B.V. All rights reserved. T