Sistemas líquido-cristalinos como potencial estratégia para administração vaginal de curcumina no tratamento da candidíase vulvovaginal
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Data
2017-06-20
Autores
Rodero, Camila Fernanda [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A candidíase vulvovaginal (CVV) é uma infecção fúngica causada principalmente pela espécie Candida albicans, sendo considerada a mais prevalente em mulheres com idade fértil, acometendo cerca de 80-85% dos indivíduos ao menos uma vez na vida. Um crescente interesse tem sido observado na utilização de compostos de origem natural, como a curcumina, de forma a atuar contra este microrganismo. Todavia, algumas de suas propriedades físico-químicas, como baixa solubilidade aquosa, dificultam a sua utilização na terapêutica. Dessa forma, a sua incorporação em sistemas líquido-cristalinos mucoadesivos (SLCM) objetivando administração vaginal pode ser uma estratégia eficiente de tratamento, de forma a potencializar a ação do fármaco, bem como oferecer maior permanência da formulação no local de ação. O objetivo deste trabalho foi desenvolver SLCM constituídos por ácido oleico e ergosterol (5:1) como fase oleosa, ácido cetílico etoxilado e propoxilado (Procetyl® AWS) como tensoativo e dispersão polimérica de quitosana (1%) como fase aquosa, acrescidos de curcumina, e caracterizá-los empregando microscopia de luz polarizada, espalhamento de raios-X de baixo ângulo (SAXS), reologia, análise de textura e mucoadesão in vitro. Posteriormente, avaliou-se a ação antimicrobiana in vitro e in vivo do sistema contra cepas de C. albicans. Pelos ensaios de microscopia de luz polarizada as formulações apresentaram estruturas semelhantes à cruz de malta e campo escuro, características de fase lamelar e microemulsões, respectivamente, resultados que foram confirmados por SAXS. Os ensaios de mucoadesão in vitro evidenciaram aumento da força mucoadesiva das formulações na presença de concentrações crescentes de muco vaginal artificial (MVA), corroborando os resultados de reologia, que evidenciaram alta viscosidade e elasticidade das formulações na presença de MVA, o que pode contribuir com a permanência da formulação no local de ação. Os resultados de ensaios microbiológicos in vitro realizados para a forma planctônica e biofilme sugerem que a curcumina teve sua ação antimicrobiana contra C. albicans potencializada mediante a sua incorporação em SLCM. Ensaios de ELISA evidenciaram diminuição das interleucinas IL-1β e TGF-β por meio do tratamento com SLCM-curcumina. O teste in vivo para a candidíase vulvovaginal (CVV) evidenciou que o SLCM-curcumina apresentou maior eficácia que o grupo controle. Os resultados sugerem que o sistema obtido apresenta potencial para incorporação de curcumina no tratamento da CVV.
Vulvovaginal candidiasis (VVC) is a fungal infection mainly caused by the Candida albicans species. The disease is being considered the most prevalent in women of childbearing age, affecting approximately 80-85% of individuals at least once in life. An increasing interest has been observed in the use of compounds of natural origin, such as curcumin, in order to act against this microorganism. However, some of its physicochemical properties, such as low aqueous solubility, make it difficult to use in therapeutics. Thus, its incorporation into mucoadhesive liquid-crystalline systems (MLCS), with vaginal administration, can be an efficient treatment strategy in order to potentiate the action of the drug, as well as to offer a longer permanence of the formulation at the site of action. The aim of this work was to develop mucoadhesive liquid-crystalline systems consisting of oleic acid and ergosterol (5: 1) as oily phase, ethoxylated and propoxylated cetylic acid (Procetyl® AWS) as a surfactant and polymer dispersion of chitosan (1%) as aqueous phase, plus curcumin and characterize them using polarized light microscopy, low-angle X-ray scattering (SAXS), rheology, texture analysis and in vitro mucoadhesion. Subsequently, the antimicrobial action in vitro and in vivo of the system against C. albicans strains was evaluated. By polarized light microscopy, the formulations presented similar structures to the cross of malt and dark field, characteristics of lamellar phase and microemulsions, respectively, the results were confirmed by low-angle X-ray scattering. In vitro mucoadhesion assays demonstrated an increase in the mucoadhesive strength of the formulations in the presence of increasing concentrations of artificial vaginal mucus (AVM), corroborating rheology results, which showed high viscosity and elasticity of the formulations in the presence of AVM, which may contribute to the permanence of the formulation at the site of action. The results of in vitro microbiological assays performed for the planktonic and biofilm form suggest that curcumin had its antimicrobial action against C. albicans potentiated by its incorporation into MLCS. ELISA assays showed a decrease in IL-1β and TGF-β interleukins by treatment with MLCS -curcumin. The in vivo test for vulvovaginal candidiasis (VVC) showed that MLCS -curcumin was more effective than the control group. The results suggest that the obtained system presents potential for incorporation of curcumin in the treatment of VVC.
Vulvovaginal candidiasis (VVC) is a fungal infection mainly caused by the Candida albicans species. The disease is being considered the most prevalent in women of childbearing age, affecting approximately 80-85% of individuals at least once in life. An increasing interest has been observed in the use of compounds of natural origin, such as curcumin, in order to act against this microorganism. However, some of its physicochemical properties, such as low aqueous solubility, make it difficult to use in therapeutics. Thus, its incorporation into mucoadhesive liquid-crystalline systems (MLCS), with vaginal administration, can be an efficient treatment strategy in order to potentiate the action of the drug, as well as to offer a longer permanence of the formulation at the site of action. The aim of this work was to develop mucoadhesive liquid-crystalline systems consisting of oleic acid and ergosterol (5: 1) as oily phase, ethoxylated and propoxylated cetylic acid (Procetyl® AWS) as a surfactant and polymer dispersion of chitosan (1%) as aqueous phase, plus curcumin and characterize them using polarized light microscopy, low-angle X-ray scattering (SAXS), rheology, texture analysis and in vitro mucoadhesion. Subsequently, the antimicrobial action in vitro and in vivo of the system against C. albicans strains was evaluated. By polarized light microscopy, the formulations presented similar structures to the cross of malt and dark field, characteristics of lamellar phase and microemulsions, respectively, the results were confirmed by low-angle X-ray scattering. In vitro mucoadhesion assays demonstrated an increase in the mucoadhesive strength of the formulations in the presence of increasing concentrations of artificial vaginal mucus (AVM), corroborating rheology results, which showed high viscosity and elasticity of the formulations in the presence of AVM, which may contribute to the permanence of the formulation at the site of action. The results of in vitro microbiological assays performed for the planktonic and biofilm form suggest that curcumin had its antimicrobial action against C. albicans potentiated by its incorporation into MLCS. ELISA assays showed a decrease in IL-1β and TGF-β interleukins by treatment with MLCS -curcumin. The in vivo test for vulvovaginal candidiasis (VVC) showed that MLCS -curcumin was more effective than the control group. The results suggest that the obtained system presents potential for incorporation of curcumin in the treatment of VVC.
Descrição
Palavras-chave
Curcumina, Sistema líquido cristalino, Mucoadesão, C. albicans, Curcumin, Liquid crystalline system, Mucoadhesion