Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos
Tuberculosis is the second leading cause of death due to the worsening of an infection in the world. An isoniazid and rifampicin are the first in the heavily affected line in the treatment and prevention of this disease. However, administration of these drugs may cause serious effects, such as pe...
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Universidade Federal do Rio Grande do Norte
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RI - UFRN |
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pt_BR |
| topic |
Tuberculose Isoniazida Rifampicina Sistema pHresponsivo Palygorskita |
| spellingShingle |
Tuberculose Isoniazida Rifampicina Sistema pHresponsivo Palygorskita Damasceno Júnior, Elmar Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| description |
Tuberculosis is the second leading cause of death due to the worsening of an infection
in the world. An isoniazid and rifampicin are the first in the heavily affected line in the
treatment and prevention of this disease. However, administration of these drugs may
cause serious effects, such as peripheral neuropathy, hepatotoxicity and
hematotoxicity, resulting from prolonged use of these substances. Thus, it is necessary
to search for new release systems for tuberculostatic drugs, in order to avoid unwanted
adverse effects, protecting or against gastrointestinal tract degradation, increasing
bioavailability and, consequently, improving therapeutic efficacy. The present work
studies the pH-responsive systems for INH and RIF, using a palygorskite as
nanocarrier, a natural, abundant and low cost material. The incorporation process was
evaluated through a factorial design, and finally investigated the influence of some
factors on drug adsorption. The experiment using a maximum concentration (0.075
mg/mL for isoniazid and 0.125 mg/mL for rifampicin), lower palygorskite mass (300
mg) and lower pH (pH 2) was the most efficient during the other experiments, resulting
in a higher dose of incorporated drug, equivalent to 12.93 mg/g palygorskite for
isoniazid and 33.62 mg/g palygorskite for rifampicin. The results obtained by the
characterization techniques (Infrared Spectroscopy with Fourier Transform, X-Ray
Diffraction, Thermogravimetry/Derivative Thermogravimetry, Differential Scanning
Calorimetry, Zeta Potential, Scanning Electron Microscopy and Dispersive Energy
Spectroscopy) and the application of kinetic and isothermal models of adsorption,
proved the incorporation of the drugs in the clay and helped to elucidate the
mechanism of interaction among the materials. Through in vitro release studies carried
out with hybrid materials, it was possible to verify the effectiveness of the pHdependent systems obtained for the drugs. More than 60% of the dose, in both cases,
was released in the intestinal medium (pH 6.8 and pH 7.4). The kinetic study showed
that the zero order model and the Higuchi model was the one that best fitted the
experimental data for isoniazid and rifampicin, respectively, indicating that the release
occurs in a prolonged way from the palygorskite. |
| author2 |
Silva, Djalma Ribeiro da |
| author_facet |
Silva, Djalma Ribeiro da Damasceno Júnior, Elmar |
| format |
masterThesis |
| author |
Damasceno Júnior, Elmar |
| author_sort |
Damasceno Júnior, Elmar |
| title |
Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| title_short |
Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| title_full |
Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| title_fullStr |
Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| title_full_unstemmed |
Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos |
| title_sort |
aplicação da palygorskita na liberação ph-responsiva de fármacos tuberculostáticos |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2021 |
| url |
https://repositorio.ufrn.br/handle/123456789/31362 |
| work_keys_str_mv |
AT damascenojuniorelmar aplicacaodapalygorskitanaliberacaophresponsivadefarmacostuberculostaticos |
| _version_ |
1773966584485773312 |
| spelling |
ri-123456789-313622021-02-07T08:26:26Z Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos Damasceno Júnior, Elmar Silva, Djalma Ribeiro da http://lattes.cnpq.br/2791074318745945 Fernandes, Nedja Suely http://lattes.cnpq.br/9563490368583906 Fonseca, José Luís Cardozo http://lattes.cnpq.br/8143800826985556 Pergher, Sibele Berenice Castella http://lattes.cnpq.br/5249001430287414 Constantino, Vera R. Leopoldo Tuberculose Isoniazida Rifampicina Sistema pHresponsivo Palygorskita Tuberculosis is the second leading cause of death due to the worsening of an infection in the world. An isoniazid and rifampicin are the first in the heavily affected line in the treatment and prevention of this disease. However, administration of these drugs may cause serious effects, such as peripheral neuropathy, hepatotoxicity and hematotoxicity, resulting from prolonged use of these substances. Thus, it is necessary to search for new release systems for tuberculostatic drugs, in order to avoid unwanted adverse effects, protecting or against gastrointestinal tract degradation, increasing bioavailability and, consequently, improving therapeutic efficacy. The present work studies the pH-responsive systems for INH and RIF, using a palygorskite as nanocarrier, a natural, abundant and low cost material. The incorporation process was evaluated through a factorial design, and finally investigated the influence of some factors on drug adsorption. The experiment using a maximum concentration (0.075 mg/mL for isoniazid and 0.125 mg/mL for rifampicin), lower palygorskite mass (300 mg) and lower pH (pH 2) was the most efficient during the other experiments, resulting in a higher dose of incorporated drug, equivalent to 12.93 mg/g palygorskite for isoniazid and 33.62 mg/g palygorskite for rifampicin. The results obtained by the characterization techniques (Infrared Spectroscopy with Fourier Transform, X-Ray Diffraction, Thermogravimetry/Derivative Thermogravimetry, Differential Scanning Calorimetry, Zeta Potential, Scanning Electron Microscopy and Dispersive Energy Spectroscopy) and the application of kinetic and isothermal models of adsorption, proved the incorporation of the drugs in the clay and helped to elucidate the mechanism of interaction among the materials. Through in vitro release studies carried out with hybrid materials, it was possible to verify the effectiveness of the pHdependent systems obtained for the drugs. More than 60% of the dose, in both cases, was released in the intestinal medium (pH 6.8 and pH 7.4). The kinetic study showed that the zero order model and the Higuchi model was the one that best fitted the experimental data for isoniazid and rifampicin, respectively, indicating that the release occurs in a prolonged way from the palygorskite. A tuberculose é a segunda maior causa de mortes ocasionadas por agravamento de uma infecção no mundo. A isoniazida e a rifampicina são fármacos de primeira linha bastante eficazes no tratamento e na prevenção dessa doença. Entretanto, a administração desses medicamentos pode ocasionar efeitos colaterais graves, como neuropatia periférica, hepatotoxicidade e hematotoxicidade, oriundos do uso prolongado dessas substâncias. Dessa forma, faz-se necessário a busca por novos sistemas de liberação para fármacos tuberculostáticos, de modo a evitar efeitos adversos indesejados, proteger o fármaco da degradação no trato gastrointestinal, aumentar a sua biodisponibilidade e, consequentemente, melhorar a sua eficácia terapêutica. O presente trabalho estudou a obtenção de sistemas pH-responsivos para isoniazida e rifampicina, utilizando a palygorskita como nanocarreador, um material natural, abundante e de baixo custo. O processo de incorporação foi avaliado por meio de um planejamento fatorial, a fim de se investigar a influência de alguns fatores na adsorção dos fármacos. O experimento utilizando a concentração máxima (0,075 mg/mL para isoniazida e 0,125 mg/mL para rifampicina), menor massa de palygorskita (300 mg) e pH mais baixo (pH 2), foi o mais eficiente perante os demais experimentos realizados, resultando em uma maior dose de fármaco incorporado, equivalente a 12,93 mg/g de palygorskita para isoniazida e 33,62 mg/g de palygorskita para rifampicina. Os resultados obtidos pelas técnicas de caracterização empregadas (Espectroscopia no Infravermelho com Transformada de Fourier, Difração de raios-X, Termogravimetria/Termogravimetria Derivada, Calorimetria Exploratória Diferencial, Potencial Zeta, Microscopia Eletrônica de Varredura e Espectroscopia de Energia Dispersiva) e pela aplicação de modelos cinéticos e isotérmicos de adsorção, comprovaram, a incorporação dos fármacos no argilomineral e ajudaram a elucidar o mecanismo de interação entre os materiais. Por meio dos estudos de liberação in vitro realizados com os materiais híbridos, conseguiu-se constatar a eficácia dos sistemas pH-dependentes obtidos para os fármacos. Mais de 60% da dose, em ambos os casos, foi liberada em meio intestinal (pH 6,8 e pH 7,4). O estudo cinético mostrou que o modelo de ordem zero e o modelo de Higuchi foi o que melhor se ajustou aos dados experimentais para a isoniazida e rifampicina, respectivamente, indicando que a liberação ocorre de forma prolongada a partir da palygorskita. 2021-02-02T23:55:44Z 2021-02-02T23:55:44Z 2020-02-04 masterThesis DAMASCENO JÚNIOR, Elmar. Aplicação da Palygorskita na liberação pH-responsiva de fármacos tuberculostáticos. 2020. 158f. Dissertação (Mestrado em Química) - Centro de Ciências Exatas e da Terra, Universidade Federal do Rio Grande do Norte, Natal, 2020. https://repositorio.ufrn.br/handle/123456789/31362 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM QUÍMICA |