Detalhes bibliográficos
| Ano de defesa: |
2021 |
| Autor(a) principal: |
Ziebarth, Jeferson
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| Orientador(a): |
Mainardes, Rubiana Mara
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| Banca de defesa: |
Não Informado pela instituição |
| Tipo de documento: |
Dissertação
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| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Estadual do Centro-Oeste
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| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química (Mestrado)
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| Departamento: |
Unicentro::Departamento de Ciências Exatas e de Tecnologia
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| País: |
Brasil
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| Palavras-chave em Português: |
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| Palavras-chave em Inglês: |
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| Área do conhecimento CNPq: |
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| Link de acesso: |
http://tede.unicentro.br:8080/jspui/handle/jspui/1838
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Resumo: |
Diabetes mellitus is a chronic non-transmissible disease that affects about 463 million people worldwide. The disease is classified into type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes, with T2DM being the most frequent in the population, accounting for about 90% of cases. Among the drugs used for the treatment of T2DM is liraglutide (LGT), used to control blood glucose by increasing the secretion of insulin by the pancreas, and is marketed in the form of a pen for subcutaneous application. Because it is a peptide, the drug, in free form, cannot be used orally, due to degradation in the gastrointestinal tract. One of the strategies used to protect and improve the oral bioavailability of drugs is the development of polymeric nanoparticles (Nps). Chitosan (CS) is a natural polymer widely used to obtain nanoparticles due to its characteristics, such as mucoadhesion, biocompatibility and non-toxicity. In this work, CS Nps containing LGT were developed by ionic gelation method using sodium tripolyphosphate (TPP) as a cross-linking agent, as an alternative for oral administration of the drug. The Nps showed a mean diameter of 323.9 nm, polydispersity index of 0.453 and zeta potential of +23.4 mV, as well as 24% encapsulation efficiency. Electron microscopy showed the spherical shape of the particles, with some irregularities and agglomerations, being characteristic of CS Nps. The physicochemical characterizations (Fourier transform infrared spectroscopy, x-ray diffraction, thermogravimetric analysis and differential scanning calorimetry) showed the CS-TPP-LGT interaction after nanoencapsulation and the amorphization of LGT in the Nps. In the stability study, it was observed that the Nps stored under refrigeration were stable for approximately 42 days, especially when evaluating the parameters mean diameter and drug content, while the Nps stored at room temperature remained stable for 30 days. The results obtained in the in vitro release assay showed that after 102h about 34,7% of LGT was released through an anomalous process, being part by diffusion and part by erosion, being the Baker-Lonsdale model the best fit for the release kinetics. The in vitro mucoadhesion assay revealed the high mucoadhesive capacity of CS Nps, with an increasing mean diameter and charge inversion from positive to negative, after contact with different mucin solutions. Therefore, it is possible to state that the nanostructured system was successfully developed and presents promising results for further work, which can be an alternative for oral drug application. |
