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Previous issue date: 2018-02-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / A Crisina (5,7-Dihidroxiflavona) pertence ? classe flavona de flavonoides. ? encontrada naturalmente em mel, pr?polis, e v?rias esp?cies de plantas, incluindo esp?cies do g?nero Pelargonium, Passiflora e da fam?lia Pinaceae. A Crisina (CS) ? atualmente comercializada como suplemento diet?tico e, como outros flavonoides, tamb?m exibe diversos efeitos farmacol?gicos, dentre os quais est?o a atividade antinociceptiva e anti-inflamat?ria. Entretanto, sua efic?cia tem sido limitada devido ? sua baixa biodisponibilidade oral. As microemuls?es (ME) s?o sistemas de libera??o modificada definidos como sistemas termodinamicamente est?veis e isotropicamente transl?cidos de dois l?quidos imisc?veis, usualmente ?gua e ?leo, estabilizados por um filme interfacial de tensoativo, e quando necess?rio um cotensoativo. Estes sistemas possuem a capacidade de solubilizar compostos hidrof?bicos, melhorar absor??o, biodisponibilidade e estabilidade, incrementar a efic?cia e reduzir a toxicidade de f?rmacos incorporados. O objetivo deste trabalho foi a obten??o, caracteriza??o de um sistema microemulsionado para incorpora??o da CS e avalia??o da atividade antinociceptiva desse. A formula??o obtida atrav?s de um diagrama de fase tern?rio foi caracterizada f?sico-quimicamente quanto ao pH, condutividade e ?ndice de refra??o. Suas caracter?sticas estruturais e morfol?gicas foram analisadas atrav?s de espalhamento de luz din?mica (DLS) e microscopia de luz polarizada (MLP). Enquanto, a estabilidade da formula??o foi avaliada atrav?s dos estudos de estresse por centrifuga??o, aquecimento-resfriamento e congelamento-descongelamento. O perfil de libera??o in vitro foi determinado utilizando o modelo de c?lulas de Franz. A avalia??o analg?sica foi realizada atrav?s de um teste comportamental que avalia o aumento do limiar de for?a sobre a pata dos camundongos para analisar o reflexo de retirada atrav?s de um analges?metro. Al?m da determina??o da capacidade de preven??o da forma??o de citocinas inflamat?rias avaliadas atrav?s de ELISA imunoensaio. Para isso foi administrada 30 minutos ap?s a indu??o por carragenina a dose de 25mg/kg de CS e MECS. A ME desenvolvida ? constitu?da por 5 % de miristato de isopropila, 55 % de ?gua e 40 % de LAS?, e apresentou pH compat?vel com a administra??o via oral, condutividade condizente com sistemas ?leo em ?gua, al?m de comportamento isotr?pico. A distribui??o de tamanho de got?culas foi do tipo monomodal e homog?neo, com tamanhos m?dios de got?culas de 170,7 ? 5,3 e 158,9 ? 26,7 nm, e potencial zeta negativo de -16,1 ? 1,9 e -10 ? 2,1, para formula??es com e sem CS, respectivamente. A ME mostrou-se est?vel frente aos estresses t?rmicos e por centrifuga??o. A libera??o in vitro da MECS obedeceu ao modelo cin?tico de ordem zero e preveniu a forma??o de citocinas inflamat?rias (redu??o de TNF ? e aumento de IL-10, p<0,01), al?m de apresentar atividade antinociceptiva no modelo de hiperalgesia induzida por carragenina (p<0,001). Portanto, p?de-se concluir que a veicula??o da CS atrav?s de um sistema microemulsionado mostrou-se como uma alternativa interessante para expandir o uso desse flavonoide como um f?rmaco no tratamento da dor inflamat?ria. / Chrysin (5,7-Dihydroxyflavone) belongs to the flavone class of flavonoids. It is found naturally in honey, propolis and various plant species, including species of the gender Pelargonium, Passiflora and the family Pinaceae. Chrysin (CS) is currently marketed as a dietary supplement and, like other flavonoids, also exhibits several pharmacological effects, among which are antinociceptive and anti-inflammatory activity. However, its efficacy has been limited because of its low oral bioavailability. Microemulsions (ME) are modified release systems defined as thermodynamically stable and isotropic translucent systems of two immiscible liquids, usually water and oil, stabilized by an interfacial surfactant film, and often a co-surfactant. ME systems have the ability to solubilize hydrophobic compounds, enhance absorption, bioavailability and stability, enhance efficacy, and reduce the toxicity of incorporated drugs. The aim of this work was the development, characterization and evaluation of the antinociceptive activity of a ME system containing CS. The formulation obtained through a ternary phase diagram was physic-chemically characterized for pH, conductivity and refractive index. Its structural and morphological characteristics were analyzed through dynamic light scattering (DLS) and polarized light microscopy (MLP). Meanwhile, the stability of the formulation was evaluated through centrifugal stress, heating-cooling and freeze-thaw studies. The in vitro release profile was determined using the Franz cell model. The analgesic evaluation was performed through a behavioral test that evaluates the increase of the force threshold on the paw of the mice to analyze the withdrawal reflex through an analgesimeter. In addition, it was determined the ability to prevent the formation of inflammatory cytokines evaluated by ELISA immunoassay. A dose of 25 mg/kg of CS and MECS was administered 30 minutes after carrageenan-induced inflammation. The developed ME consists of 5% isopropyl myristate, 55% water and 40% LAS?, and presented pH compatible with oral administration, conductivity consistent with oil-in-water systems, as well as isotropic behavior. The droplet size distribution was of the monomodal and homogeneous type, with mean droplet sizes of 170.7 ? 5.3 and 158.9 ? 26.7 nm, and negative zeta potential of -16.1 ? 1.9 and -10 ? 2.1, for formulations with and without CS, respectively. ME was stable during the thermal stresses and centrifugation. The in vitro release of MECS followed the zero order kinetic model and prevented the formation of inflammatory cytokines (reduction of TNF? and increase of IL-10, p<0.01), as well as antinociceptive activity in carrageenan-induced inflammation model (p<0.001). Therefore, CS delivery through a microemulsion system proved to be an interesting alternative to expand the use of this flavonoid as a drug in the treatment of inflammatory pain.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/24987 |
| Date | 22 February 2018 |
| Creators | Ramalho, ?zola Morais de Medeiros |
| Contributors | 99328976472, Soares Sobrinho, Jos? Lamartine, 00816243441, Lemos, Telma Maria Ara?jo Moura, 70155780425, Silva J?nior, Arn?bio Antonio da, Lima, Adley Antonini Neves de |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM CI?NCIAS FARMAC?UTICAS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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