title: Pomegranate seed oil nanoemulsions improve the photostability and in vivo antinociceptive effect of a non-steroidal anti-inflammatory drug.
abstract: The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Luana Mota
authors.initials: LM
authors.lastname: Ferreira
authors.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Marcel Henrique Marcondes
authors.initials: MHM
authors.lastname: Sari
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Verônica Ferrari
authors.initials: VF
authors.lastname: Cervi
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Mailine
authors.initials: M
authors.lastname: Gehrcke
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Allanna Valentini
authors.initials: AV
authors.lastname: Barbieri
authors.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Vanessa Angonesi
authors.initials: VA
authors.lastname: Zborowski
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ruy Carlos Ruver
authors.initials: RCR
authors.lastname: Beck
authors.affiliation: Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
authors.forename: Cristina Wayne
authors.initials: CW
authors.lastname: Nogueira
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: leticiacruz@smail.ufsm.br.
authors.forename: Letícia
authors.initials: L
authors.lastname: Cruz
mesh_terms: D000005:Abdomen / Q000473:pathology; D019342:Acetic Acid; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003251:Constriction, Pathologic; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry*; D005620:Freund's Adjuvant; D007249:Inflammation / Q000150:complications / Q000188:drug therapy; D007267:Injections; D007660:Ketoprofen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010146:Pain / Q000150:complications / Q000188:drug therapy; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds / Q000737:chemistry; D023382:Toxicity Tests, Acute; D014466:Ultraviolet Rays
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004655:Emulsions; D010938:Plant Oils; D005620:Freund's Adjuvant; D007660:Ketoprofen; D019342:Acetic Acid
keywords: Antinociceptive effect; Ketoprofen; Nanoemulsions; Photostability; Pomegranate seed oil