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Previous issue date: 2011-07-11 / The aim of this work was to evaluate how an aqueous micellar system containing
Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating
treatment. Also a review of the literature about the new physicochemical and biological
properties of this new system was carried out. Afterwards, heated (AmB-DOC-H) and
unheated (AmB-DOC) micelles were subsequently diluted at four different
concentrations (50mg.L-1, 5mg.L-1, 0.5mg.L-1 and 0.05mg.L-1) to perform the
physicochemical study and, then, the pharmacotoxicity assay, in which two cell models
were used for the in vitro experiments, Red Blood Cells (RBC) from human donors and
Candida parapisilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC
were the used parameters to evaluate the acute and chronic toxicity, respectively, the
efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival
rate from Cp. The spectral study revealed a slight change on the aggregate peak from
327nm to 323nm for AmB-DOC-H compared to AmB-DOC. Concerning the toxicity,
although AmB-DOC and AmB-DOC-H presented different behavior for hemoglobin
leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations
(from 5mg.L-1) with values tending to zero. However, concerning K+ leakage, both
AmB-DOC and AmB-DOC-H, showed similar profile for both cell models, RBC and Cp
(p<0,05). AmB-DOC-H and AmB-DOC also revealed similar profile of activity against Cp
with equivalent survival rate. In short, the AmB-DOC-H showed much less toxicity than
AmB-DOC, but remained as active as the late one against fungal cell. Therefore, the
results highlight the importance of this new procedure as a simple, inexpensive and safe
alternative to produce a new kind of micelle system for treatment of systemic fungal
infections / A anfotericina B micelar (AmB) ? um importante agente antimicrobiano utilizado contra
infec??es f?ngicas sist?micas. No entanto, seu uso ? limitado devido a sua alta
toxicidade. Formula??es de anfotericina B em estruturas lip?dicas s?o menos t?xicas,
por?m apresentam elevado custo. A AmB em solu??o aquosa possui formas
monom?ricas e agregadas, estes ?ltimos s?o os respons?veis pelas rea??es adversas.
Este trabalho avaliou a AmB desoxicolato de s?dio (AmB-DOC) e AmB aquecida (AmBDOC-
H) em rela??o a sua toxicidade e atividade, bem como perfil de seu espectro em
quatro concentra??es diferentes (50mg.L-1, 5mg.L-1, 0,5mg.L-1 e 0.05mg.L-1). O
aquecimento controlado das solu??es AmB levou a altera??es no espectro de 327nm
AmB (agregados) para 323nm (superagregados). Al?m disso, quando as amostras
foram submetidas ao processo de dilui??o, apresentam o mesmo comportamento
espectrofotom?trico: ambas as amostras diminuem o pico das formas auto-associadas
at? apresentarem apenas mon?meros com pico em 409nm, o que sugere um processo
de libera??o de mon?meros por concentra??o-dependente. No que diz respeito ?
toxicidade, AmB-DOC e AmB-DOC-H apresentaram comportamentos distintos: a taxa
de libera??o de hemoglobina de hem?cias para AmB-DOC, em altas concentra??es, foi
muito superior a AmB-DOC-H, cujos valores tendem a zero (p <0,05). J? em rela??o ?
libera??o de K+ ambas as amostras apresentaram perfil semelhante. Sobre a atividade,
AmB-H mant?m o mesmo perfil da AmB-DOC. Em suma, a AmB-DOC-H ? muito
menos t?xica do que AmB-DOC e mantendo a atividade. Sendo este procedimento
uma alternativa simples, de baixo custo e segura para, em um o futuro pr?ximo, ser
utilizada no tratamento de infec??es f?ngicas sist?micas
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13349 |
| Date | 11 July 2011 |
| Creators | Silva Filho, Miguel Adelino da |
| Contributors | CPF:38878240400, http://lattes.cnpq.br/6907806915889763, Maranh?o, Raul Cavalcante, CPF:03312356172, http://lattes.cnpq.br/5014918663341911, Damasceno, Bolivar Ponciano Goulart de Lima, CPF:91616751487, http://lattes.cnpq.br/6407334157973308, Egito, Eryvaldo S?crates Tabosa do |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias da Sa?de, UFRN, BR, Ci?ncias da Sa?de |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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