title: Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells.
abstract: BACKGROUND
  Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment.
  
  
  OBJECTIVE
  The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells.
  
  
  METHODS
  NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model.
  
  
  RESULTS
  Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately.
  
  
  CONCLUSIONS
  Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Luana
authors.initials: L
authors.lastname: Mota Ferreira
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Mailine
authors.initials: M
authors.lastname: Gehrcke
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Verônica
authors.initials: V
authors.lastname: Ferrari Cervi
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Paula
authors.initials: P
authors.lastname: Eliete Rodrigues Bitencourt
authors.affiliation: b Programa de Pós-Graduação em Bioquímica e Bioprospecção , Centro de Ciências Químicas, Farmacêuticas e de Alimentos , Pelotas , Brazil.
authors.forename: Elita
authors.initials: E
authors.lastname: Ferreira da Silveira
authors.affiliation: b Programa de Pós-Graduação em Bioquímica e Bioprospecção , Centro de Ciências Químicas, Farmacêuticas e de Alimentos , Pelotas , Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Hofstatter Azambuja
authors.affiliation: c Curso de Biomedicina , Centro Universitário Franciscano , Santa Maria , Brazil.
authors.forename: Andiara
authors.initials: A
authors.lastname: Prates Ramos
authors.affiliation: c Curso de Biomedicina , Centro Universitário Franciscano , Santa Maria , Brazil.
authors.forename: Kátia
authors.initials: K
authors.lastname: Nascimento
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Maria
authors.initials: M
authors.lastname: Beatriz Moretto
authors.affiliation: b Programa de Pós-Graduação em Bioquímica e Bioprospecção , Centro de Ciências Químicas, Farmacêuticas e de Alimentos , Pelotas , Brazil.
authors.forename: Elizandra
authors.initials: E
authors.lastname: Braganhol
authors.affiliation: c Curso de Biomedicina , Centro Universitário Franciscano , Santa Maria , Brazil.
authors.forename: Michele
authors.initials: M
authors.lastname: Rorato Sagrillo
authors.affiliation: a Programa de Pós-graduação em Ciências Farmacêuticas , Centro de Ciências da Saúde, Universidade Federal de Santa Maria , Santa Maria , Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Cruz
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003603:Cytotoxins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004655:Emulsions / Q000494:pharmacology / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D029561:Lythraceae; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D012639:Seeds
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003603:Cytotoxins; D004655:Emulsions; D010936:Plant Extracts; D010938:Plant Oils
keywords: Antitumor effect; C6 cells; astrocyte cells; catalase activity; colloidal systems; comet assay; lipid peroxidation; protein carbonylation; punica granatum