Detalhes bibliográficos
| Ano de defesa: |
2013 |
| Autor(a) principal: |
CARRARO, TALITA CRISTINA MOREIRA MORAES
 |
| Orientador(a): |
Mainardes, Rubiana Mara
|
| Banca de defesa: |
Não Informado pela instituição |
| Tipo de documento: |
Dissertação
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Universidade Estadual do Centro-Oeste
|
| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Farmacêuticas (Mestrado / Associação Ampla com UEPG)
|
| Departamento: |
Unicentro::Departamento de Farmácia
|
| País: |
Brasil
|
| Palavras-chave em Português: |
|
| Área do conhecimento CNPq: |
|
| Link de acesso: |
http://tede.unicentro.br:8080/jspui/handle/jspui/655
|
Resumo: |
Amphotericin B (AFB) is a broad spectrum antifungal drug and widely used in the treatment of systemic fungal infections. However, through the administration of conventional formulations have adverse effects mainly associated cytotoxicity which limit its use and therapeutic efficacy. In this study, polymeric nanoparticles (NP´s) containing AFB were developed, with the goal of reducing toxicity to human cells and maintenance the therapeutic effectiveness of the drug. The nanoparticles were successfully obtained by the emulsification/ solvent evaporation method, employing the copolymer poly (lactic-co-glycolic acid) (PLGA), and blends of PLGA and polyethylene glycol (PEG). A factorial design was conducted and through it was possible to establish the optimal composition which obtained particles with reduced diameters (< 200 nm) and high rates of drug encapsulation efficiency (> 89%). For quantification of AFB in solution, an analytical method by high performance liquid chromatography (HPLC) was developed and validated according to present norms. The physic-chemical characterization included analysis by X-ray diffraction, which showed amorphous pattern in the indicating the NP´s of an inclusion complex in which the drug is molecularly dispersed. The results of the antifungal efficacy and cytotoxicity in vitro indicate that, despite the presence of molecular oligomers of AFB in the formulations, nanoparticles showed lower toxicity on cells compared to commercial standard and the free drug and maintained the antifungal activity forward a strains of C. albicans and Cryptococcus neoformans. Through the in vivo experiment, the administration of PLGA and PLGA-PEG NP´s containing AFB, orally and intraperitonially, provided no significant change in blood profile, plasma levels of creatinine, urea, AST and ALT. Comparing commercial standard of the drug, the histopathological tests indicated that the NP's protected the liver tissue damage caused by AFB. Thus, it is concluded that NP's containing AFB developed in this study have suitable physicochemical characteristics, which make them a potential drug delivery systems of the drug, maintaining the antifungal efficacy and minimizing cytotoxicity against the commercial standard. |
