title: Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential.
abstract: OBJECTIVE
  The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays.
  
  
  METHODS
  The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays.
  
  
  RESULTS
  In vivo assays were conducted for the first time in order to assess the LDH-Mef potential. The hemolytic effects decreased for the intercalated Mef as demonstrated by the higher tolerated hemolytic concentration (1.83 mM) compared to mefenamic acid (MefH), 0.48 mM. Pretreatment of animals with MefH or LDH-Mef reduced carrageenan-, dextran sulfate- and PGE2-induced paw edema. MefH or LDH-Mef also decrease total leucocytes and neutrophil counts of the peritoneal cavity after inflammation induction with carrageenan. In the nociception model, oral pretreatment with LDH-Mef reduced mechanical hypernociception carrageenan-induced after 3-4h and also the number of writhings induced by acetic acid.
  
  
  CONCLUSIONS
  This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect.
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, USP, Av. Prof. Lineu Prestes 748, 05508-000 São Paulo, São Paulo, Brazil.
authors.forename: Vanessa R R
authors.initials: VR
authors.lastname: Cunha
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970, Campinas, São Paulo, Brazil.
authors.forename: Viviane A
authors.initials: VA
authors.lastname: Guilherme
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970, Campinas, São Paulo, Brazil.
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
authors.affiliation: Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970, Campinas, São Paulo, Brazil; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210-170 Santo André, São Paulo, Brazil.
authors.forename: Daniele R
authors.initials: DR
authors.lastname: de Araujo
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus de Parnaíba, Universidade Federal do Piauí, UFPI, 64202020 Parnaíba, Piauí, Brazil.
authors.forename: Renan O
authors.initials: RO
authors.lastname: Silva
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus de Parnaíba, Universidade Federal do Piauí, UFPI, 64202020 Parnaíba, Piauí, Brazil.
authors.forename: Jand V R
authors.initials: JV
authors.lastname: Medeiros
authors.affiliation: Núcleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus de Parnaíba, Universidade Federal do Piauí, UFPI, 64202020 Parnaíba, Piauí, Brazil.
authors.forename: José R S A
authors.initials: JR
authors.lastname: Leite
authors.affiliation: Departamento de Física dos Materiais e Mecânica, Instituto de Física, Universidade de São Paulo, USP, 05315-970 São Paulo, São Paulo, Brazil.
authors.forename: Philippe A D
authors.initials: PA
authors.lastname: Petersen
authors.affiliation: School of Pharmacy, University of Waterloo, N2L 3G1 Waterloo, Ontario, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
authors.affiliation: Departamento de Física dos Materiais e Mecânica, Instituto de Física, Universidade de São Paulo, USP, 05315-970 São Paulo, São Paulo, Brazil.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Petrilli
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, USP, Av. Prof. Lineu Prestes 748, 05508-000 São Paulo, São Paulo, Brazil.
authors.forename: Vera R L
authors.initials: VR
authors.lastname: Constantino
mesh_terms: D000700:Analgesics / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008528:Mefenamic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D006878:Hydroxides; D008528:Mefenamic Acid; D002351:Carrageenan
keywords: Anti-inflammatory; Antinociceptive; Density functional theory; Layered double hydroxide; Mefenamic acid