Desenvolvimento e avaliação de um sistema de liberação sustentada de gentamicina em biomembranas de látex natural
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Data
2016-03-15
Autores
Gemeinder, José Lúcio Pádua [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Sistemas de liberação de fármacos são fundamentais para promoção de ações terapêuticas, dentre eles os sistemas transdérmicos que representam uma alternativa frente às propriedades farmacocinéticas e farmacodinâmicas dos fármacos. Através deste sistema é possível controlar sua liberação e manter a concentração por um longo período. Devido a ascendência da população idosa e das enfermidades que os acometem, o desenvolvimento destes sistemas é primordial para uma melhor adesão e conforto do paciente. Atualmente, diversos polímeros, principalmente os naturais, são usados para este fim. A membrana látex natural (NRL) extraído da seringueira Hevea brasiliensis, destaca-se por suas propriedades físicas, por ser um polímero renovável e extensamente utilizado para a produção de biomembranas. Vários estudos demonstraram atividades angiogênicas, de neovascularização, e de reparação tecidual deste biopolímero. O sulfato de gentamicina, um antimicrobiano da classe dos aminoglicosídeos, inibe o crescimento de vários micro-organismos Gram-positivos e Gram-negativos, agindo principalmente na inibição da síntese proteica bacteriana por ligação ribossomal (30S). Neste sentido, o objetivo deste estudo foi desenvolver um novo sistema de liberação sustentada incorporando o sulfato de gentamicina ao látex natural, utilizando-o como carreador do fármaco, aumentando a atividade deste biopolímero. Com o intuito de caracterizar as propriedades físico-química das biomembranas, foram utilizados alguns métodos como a microscopia eletrônica por varredura (MEV), resistência mecânica e a espectroscopia por infravermelho (FTIR-ATR), antes e após da incorporação do fármaco. Buscou-se entender o comportamento da taxa de liberação frente aos diferentes meios e verificar a atividade antimicrobiana após incorporação do fármaco no látex. As biomembranas foram preparadas por casting, em moldes de teflon®, seguida de secagem à temperatura ambiente. A imagem da MEV demonstrou a incorporação da gentamicina ao látex, observada na superfície da biomembrana. A resistência mecânica mostrou um aumento na tensão máxima com a incorporação da gentamicina quando comparada ao látex puro, apesar de não ter havido alteração no módulo de Young, 1,3 – 1,9 Mpa, valores reportados na literatura para NRL. Observou-se que no FTIR-ATR não houve mudança nos espectros após a mistura dos compostos, uma vez que as bandas de absorção foram preservadas e não houve novos picos. Com a liberação do fármaco em diferentes meios, durante 6 dias, foi possível constatar uma variação do burst release e do tempo de liberação, no qual destaca-se uma maior liberação em meio ácido e básico devido a uma maior biodisponibilidade de absorção nestes meios. O látex não alterou a atividade antimicrobiana da gentamicina frente às cepas de Staphylococcus aureus e Escherichia coli, predominante em infecções por queimaduras e feridas, apresentando respectivamente halos de inibição de 28,4 mm e 19,5 mm frente aos 15,0 mm referidos na literatura. Estes resultados reforçam que o látex pode ser usado como um carreador de fármacos, mostrando ser uma alternativa interessante de curativo/adesivo para uso tópico.
Drug delivery systems (DDS) are fundamental to promoting therapeutic actions, including transdermal systems that represent an alternative for pharmacokinetic and pharmacodynamic drugs properties. Through this system it is possible to control its release and to maintain its concentration for a long period. Due to population ageing and the diseases that affect them, the development of these systems is the key to improve compliance and patient comfort. Nowadays, many polymers, especially from natural source are used for this purpose. The natural rubber latex (NRL) extracted from Hevea brasiliensis stands out for its physical properties, for being a renewable polymer and widely used for the biomembranes production. Several studies have showed angiogenic and neovascularization activities besides tissue repair of this biopolymer. Gentamicin sulfate, an aminoglycosides class antimicrobial, inhibits the growth of several Gram-positive and Gram-negative microorganisms, acting in the bacterial protein synthesis through ribosomal biding (30S). Therefore, the aim of this study was to develop a new sustained gentamicin sulfate release system using NRL as a drug carrier, increasing the activity of this biopolymer. In order to characterize the biomembranes physicochemical properties, they were analyzed by some methods like scanning electron microscopy (SEM), mechanical strength (by tension) and infrared spectroscopy (FTIR-ATR), before and after the drug incorporation. In addition, it was attempted to understand the release rate behavior among the different media and to verify the antimicrobial activity of the drug after its incorporation into the latex. The biomembranes were prepared by casting on Teflon® mold, and then dried at room temperature. The SEM micrographs proved the incorporation of the gentamicin into the latex, observed at the biomembrane surface. The mechanical strength showed an increase in the maximum stress with the gentamicin incorporation when compared to pure latex, although there have been no change in the Young`s modulus between 1.3-1.9 MPa, values reported in the literature for the NRL. It was observed in the FTIR-ATR that there was no change in the spectra after mixing the compounds, since the absorption bands have been preserved and there were no new peaks. The release of the drug in different media, for 6 days, showed a variation in the time and in the burst release, which highlights a higher release in acid and base media due to a higher absorption bioavailability in these media. The latex did not change the gentamicin antimicrobial activity against Staphylococcus aureus and Escherichia coli strains, prevalent in burns and wounds infections, showing inhibition halos of 28.4 mm and 19.5 mm against the 15.0 mm literature referred. These results emphasize that the NRL can be used as a drug carrier, showing to be an interesting alternative of a dressing/adhesive for topical use.
Drug delivery systems (DDS) are fundamental to promoting therapeutic actions, including transdermal systems that represent an alternative for pharmacokinetic and pharmacodynamic drugs properties. Through this system it is possible to control its release and to maintain its concentration for a long period. Due to population ageing and the diseases that affect them, the development of these systems is the key to improve compliance and patient comfort. Nowadays, many polymers, especially from natural source are used for this purpose. The natural rubber latex (NRL) extracted from Hevea brasiliensis stands out for its physical properties, for being a renewable polymer and widely used for the biomembranes production. Several studies have showed angiogenic and neovascularization activities besides tissue repair of this biopolymer. Gentamicin sulfate, an aminoglycosides class antimicrobial, inhibits the growth of several Gram-positive and Gram-negative microorganisms, acting in the bacterial protein synthesis through ribosomal biding (30S). Therefore, the aim of this study was to develop a new sustained gentamicin sulfate release system using NRL as a drug carrier, increasing the activity of this biopolymer. In order to characterize the biomembranes physicochemical properties, they were analyzed by some methods like scanning electron microscopy (SEM), mechanical strength (by tension) and infrared spectroscopy (FTIR-ATR), before and after the drug incorporation. In addition, it was attempted to understand the release rate behavior among the different media and to verify the antimicrobial activity of the drug after its incorporation into the latex. The biomembranes were prepared by casting on Teflon® mold, and then dried at room temperature. The SEM micrographs proved the incorporation of the gentamicin into the latex, observed at the biomembrane surface. The mechanical strength showed an increase in the maximum stress with the gentamicin incorporation when compared to pure latex, although there have been no change in the Young`s modulus between 1.3-1.9 MPa, values reported in the literature for the NRL. It was observed in the FTIR-ATR that there was no change in the spectra after mixing the compounds, since the absorption bands have been preserved and there were no new peaks. The release of the drug in different media, for 6 days, showed a variation in the time and in the burst release, which highlights a higher release in acid and base media due to a higher absorption bioavailability in these media. The latex did not change the gentamicin antimicrobial activity against Staphylococcus aureus and Escherichia coli strains, prevalent in burns and wounds infections, showing inhibition halos of 28.4 mm and 19.5 mm against the 15.0 mm literature referred. These results emphasize that the NRL can be used as a drug carrier, showing to be an interesting alternative of a dressing/adhesive for topical use.
Descrição
Palavras-chave
Biomembrana de látex natural, Liberação sustentada, Atividade antimicrobiana, Biomaterial, Liberação de Fármaco, Natural Rubber Latex, Sustained Release, Antimicrobial Activity, Biomaterial, Drug Release