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Previous issue date: 2017-02-02 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Doen?as negligenciadas, incluindo a doen?a de Chagas, representam um problema de sa?de
mundial devido ao desinteresse da ind?stria na pesquisa por novos f?rmacos. Benznidazol
(BNZ), f?rmaco dispon?vel no Brasil para o tratamento da doen?a de Chagas, e distribu?do
pelo Minist?rio da Sa?de, apresenta algumas limita??es quanto ao seu uso, em especial na
fase cr?nica da doen?a. A tecnologia farmac?utica proporciona o desenvolvimento de
sistemas que aumentam a solubilidade do f?rmaco ou aumento de sua concentra??o nas
c?lulas/tecidos infectados o que reflete diretamente no aumento da biodisponibilidade e
efici?ncia terap?utica do BNZ. Assim, sistemas l?quidos tais como os sistemas coloidais
lip?dicos (SCL), como emuls?es, microemuls?es, nanoemuls?es s?o uma alternativa
interessante para o aumento da biodisponilidade oral e parenteral do BNZ. Este trabalho tem
como objetivo o desenvolvimento de nanoemuls?es biocompat?veis contendo triglicer?deo de
cadeia m?dia (Miglyol?812) estabilizados por uma mistura adequada de tensoativos
(fosfatidilcolina de soja e oleato de s?dio), al?m de avaliar o efeito tripanocida. As condi??es
ideais para obten??o dos sistemas de interesse foi avaliada pelo estudo da temperatura de
invers?o de fases (TIF) e da adi??o de um novo componente. Nanoemuls?es foram formadas
com adi??o de 2-metilpirrolidona (NMP) com tamanho de got?cula uniforme e menor que
162,66 nm. Os sistemas permaneceram est?veis at? 60 dias quando armazenados a
temperatura de 25 ?C. As propriedades reol?gicas mostraram comportamento dependente com
a quantidade de co-solvente adicionada ao sistema. As imagens de microscopia de luz
polarizada e espalhamento de raios-X a baixo ?ngulo confirmaram a forma??o de sistemas
isotr?picos quando o co-solvente est? em concentra??o superior a 5%. A libera??o de BNZ
nos sistemas contendo ?cido si?lico em diferentes concentra??es, foi at? 3 (tr?s) vezes mais
r?pida que os sistemas sem a subst?ncia. Os sistemas apresentaram biocompatibilidade em
diferentes linhagens celulares (Vero, SiHa e LLC-MK2). Nanoemuls?es apresentaram
capacidade de veicular o BNZ em sistemas biocompat?veis e com excelente atividade
tripanocida, representando assim um futuro promissor no tratamento da doen?a de Chagas,
considerando que at? o presente n?o existem formas farmac?uticas l?quidas de administra??o,
o que impossibilita o ajuste da dose e a redu??o de efeitos colaterais. / Neglected diseases, including Chagas disease, represent a global health problem due to the
industry's lack of interest in research for new drugs. Benznidazole (BNZ), a drug available in
Brazil for the treatment of Chagas disease, and distributed by the Health Ministery, presents
some limitations regarding its use, especially in the chronic phase of the disease.
Pharmaceutical technology provides the development of systems that increase drug solubility
or increase its concentration in infected cells / tissues which directly reflects the increased
bioavailability and therapeutic efficacy of BNZ. Thus, liquid systems such as lipid colloidal
systems (LCS), such as emulsions, microemulsions, nanoemulsions are an interesting
alternative for increasing oral and parenteral bioavailability of BNZ. This work aims to
develop biocompatible nanoemulsions containing medium chain triglycerides (Miglyol?812)
stabilized by a suitable mixture of surfactants (soybean phosphatidylcholine and sodium
oleate), and to evaluate the trypanocidal effect. The ideal conditions for obtaining the systems
of interest were evaluated by the study of phase inversion temperature (PIT) and the addition
of a new component. Nanoemulsions were formed with addition of 2-methylpyrrolidone
(NMP) with uniform droplet size and less than 162.66 nm. The systems remained stable for
up to 60 days when stored at 25 ? C. The rheological properties showed a behavior dependent
on the amount of co-solvent added to the system. The polarized light microscopy and low
angle X-ray scattering images confirmed the formation of isotropic systems when the
cosolvent is in a concentration greater than 5%. The release of BNZ in systems containing
sialic acid at different concentrations was up to 3 (three) times faster than systems without the
substance. The systems showed biocompatibility in different cell lines (Vero, SiHa and LLCMK2).
Nanoemulsions were able to transport BNZ in biocompatible systems with excellent
trypanocidal activity, thus representing a promising future in the treatment of Chagas' disease,
considering that to date there are no liquid dosage forms of administration, which makes it
impossible to adjust the dose and decrease of side effects.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/22720 |
| Date | 02 February 2017 |
| Creators | Streck, Let?cia |
| Contributors | 00840406452, http://lattes.cnpq.br/2593509584288129, C?mara, Antonia Claudia J?come da, 43007600472, http://lattes.cnpq.br/5445255186647578, Fonseca, Jos? Luis Cardozo, 90623207753, http://lattes.cnpq.br/8143800826985556, Souza, Rog?ria Nunes de, 74511521468, http://lattes.cnpq.br/3881220392537924, Sarmento, Victor Hugo Vitorino, 16255241882, http://lattes.cnpq.br/2008100603446246, Silva J?nior, Arnobio Antonio da |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM DESENVOLVIMENTO E INOVA??O TECNOL?GICA EM MEDICAMENTOS, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| 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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