Desenvolvimento, caracterização e avaliação biológica de implantes poliméricos biodegradáveis contendo sirolimus
Ano de defesa: | 2018 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Minas Gerais
UFMG |
Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | http://hdl.handle.net/1843/BUOS-B4ZMF4 |
Resumo: | The implantable polymeric systems are able to provide the drug directly at site of action at therapeutic doses over a prolonged period, representing an innovative dosage form of treatment. The poly-lactic-co-glycolic acid is a biodegradable synthetic polymer with high biocompatibility. For this reason, it has been used extensively in release drug delivery systems. Sirolimus is a macrocyclic antibiotic which has immunosuppressive activity. Its action involves the inhibition of a kinase involved in lymphocyte proliferation. Even though, sirolimus has undesirable characteristics regarding its administration by its side effects. Thus, the purpose of this report was the development, characterization and biological evaluation of poly-lactide-co-glycolide implants loaded with sirolimus. Implants were prepared by the hot molding technique and characterized by fourier transform infrared spectroscopy, thermal analysis and X-ray diffraction. To evaluate the in vivo release profile of the implants, Swiss mice received subcutaneous implants containing 25% (w / w) of sirolimus and implants without the drug. The drug levels were determined during a 42-day study period and the biodegradation was evaluated after 7, 14 and 28 days by stereomicroscopy and scanning electron microscopy. After 7 and 42 days of the in vivo release study, the skin of the implanted site was sampled for histopathological evaluation. The anti-inflammatory activity of the systems was evaluated in a model of fibrovascular tissue formation induced by the subcutaneous implantation of a cotton pellet, in mice. The results demonstrated the thermal stability of the constituents up to 190°C. Changes in the crystalline structure of the drug and in the amorphous structure of the polymer during the process of implants production were observed. No chemical modifications and incompatibility between the drug and the polymer were visualized. The biological evaluation showed that the implants are able to release sirolimus for a prolonged time, in an amount able to reduce the chronic inflammatory response in the evaluated model. Thus, these preliminary findings indicate that the implants developed in this study were safe for the experimental animals and may be a promising alternative for sirolimus delivery, to be used in the therapeutic management of different chronic diseases, especially which have an associated inflammatory process. |