Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp Characterization and evaluation of nanoencapsulated diethylcarbamazine in model of acute hepatic inflammation Gabriel Barros Rodrigues a,b , Elquio Eleamen Oliveira c , Francisco Jaime Bezerra Mendonça Junior c , Laise Aline Martins dos Santos a , Wilma Helena de Oliveira a,b , Maria Eduarda Rocha de França a,b , Deniele Bezerra Lós a,d , Brennda Martins Gabínio c , Fábia Cristiane Melo Leite de Lira e , Christina Alves Peixoto a,⁎ a Laboratório de Ultraestrutura, Instituto Aggeu Magalhães – FIOCRUZ, Recife, Brazil b Programa de Pós-graduação em Ciências Biológicas, Centro de Biociências, Universidade Federal de Pernambuco - UFPE, Recife, Brazil c Laboratório de Síntese e Vetorização de Moléculas (LSVM), Universidade Estadual da Paraíba, João Pessoa, Brazil d Programa de Pós-graduação em Biotecnologia/RENORBIO, Universidade Federal de Pernambuco - UFPE, Recife, Brazil e Laboratório de Biologia Celular e Ultraestrutura, Centro de Tecnologias Estratégicas do Nordeste – CETENE, Recife, Brazil ARTICLE INFO Keywords: Diethylcarbamazine Nanoencapsulation Liver Inflammation Carbon tetrachloride ABSTRACT Previous studies from our laboratory have demonstrated that Diethylcarbamazine (DEC) is a potent anti-in- flammatory drug. The aim of the present study was to characterize the nanoencapsulation of DEC and to evaluate its effectiveness in a model of inflammation for the first time. C57BL/6 mice were divided into six groups: 1) Control; 2) Carbon tetrachloride (CCl4); 3) DEC 25 mg/kg + CCl4; 4) DEC 50 mg/kg + CCl4; 5) DEC-NANO 05 mg/kg + CCl4 and 6) DEC-NANO 12.5 mg/kg + CCl4. Liver fragments were stained with hematoxylin-eosin, and processed for Western blot, ELISA and immunohistochemistry. Serum was also collected for biochemical measurements. Carbon tetrachloride induced hepatic injury, observed through increased inflammatory markers (TNF-α, IL-1β, PGE2, COX-2 and iNOS), changes in liver morphology, and increased serum levels of total cholesterol, triglycerides, TGO and TGP, LDL, as well as reduced HDL levels. Nanoparticles containing DEC were characterized by diameter, polydispersity index and zeta potential. Treatment with 12.5 nanoencapsulated DEC exhibited a superior anti-inflammatory action to the DEC traditional dose (50 mg/kg) used in murine assays, restoring liver morphology, improving serological parameters and reducing the expression of inflammatory markers. The present formulation of nanoencapsulated DEC is therefore a potential therapeutic tool for the treatment of inflammatory hepatic disorders, permitting the use of smaller doses and reducing treatment time, while maintaining high efficacy. 1. Introduction Acute hepatitis can occur without symptoms and may lead to high blood bilirubin levels (jaundice), a decreased sensation of appetite, and fatigue. About 90% of patients with acute hepatitis recover sponta- neously. However, depending on the type and duration of the stimulus, the disease may progress to a serious condition, such as acute liver failure (ALF). ALF is characterized by acute inflammation with severe liver cell injury, where a previously normal liver fails within days or weeks. With a high mortality rate (40–50%), drug-induced injury is responsible for half the cases of ALF [1,2]. The hepatotoxin carbon tetrachloride (CCl 4 ) is widely used in models of liver inflammation. CCl 4 causes fatty liver, acute necrosis and oxidative stress. Studies have demonstrated that single doses of CCl 4 cause areas of necrosis and the generation of reactive radicals in 2 h following administration [3,4]. Diethylcarbamazine (DEC) is a piperazine derivative which, as a result of its microfilaricide action, has been used in the treatment and control of lymphatic filariasis since 1947. DEC also has anti-in- flammatory properties due to its interference with arachidonic acid metabolism. Studies demonstrate the inhibition of enzymes of the 5- lipoxygenase pathway and cyclooxygenase, resulting in a reduction in prostaglandin E2 (PGE 2 ) production [5]. In a previous study, we characterized the anti-inflammatory action of DEC in a liver model of chronic inflammation induced by alcohol. The results demonstrated that treatment with 50 mg/kg of DEC for http://dx.doi.org/10.1016/j.intimp.2017.07.014 Received 12 May 2017; Received in revised form 11 July 2017; Accepted 13 July 2017 ⁎ Corresponding author at: Instituto Aggeu Magalhães, Av Moraes Rego s/n Campus da UFPE FIOCRUZ, Recife CEP 52171-011, Brazil. E-mail address: cpeixoto@cpqam.fiocruz.br (C.A. Peixoto). International Immunopharmacology 50 (2017) 330–337 1567-5769/ Published by Elsevier B.V. MARK