Orientador(a): Prof(a). Dr(a). Juliana Marchi / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2016. / A osteomielite e uma inflamacao ossea frequente em traumas diversos, causada por
um organismo infectante. O tratamento convencional e o debridamento do osso
infectado e dos tecidos moles adjacentes, associado a administracao de antibiotico via
sistemica. Este estudo caracterizou o sistema injetavel a base de poloxamer 407
(PL407) . sozinho ou combinado com poloxamer 188 (PL188) . incorporado com o
antibiotico teicoplanina e diferentes composicoes de ¿À-TCP (¿À-TCP) dopados com
magnesio e/ou zinco, proposto como uma alternativa para o tratamento de osteomielite
associada a reparacao ossea. As formulacoes foram caracterizadas por analise
estrutural, determinacao da temperatura de transicao sol-gel, avaliacao do perfil de
dissolucao das formulacoes e de liberacao da teicoplanina in vitro, e caracterizacao
biologica in vitro. Os resultados mostraram que a adicao dos fosfatos tricalcicos e da
teicoplanina nao alteraram a reversibilidade termica dos poloxamers, mas a teicoplanina
diminuiu as temperaturas de transicao sol-gel. As formulacoes mantiveram uma das
caracteristicas vantajosas dos poloxamer: a capacidade de serem injetados na forma
liquida na temperatura ambiente e gelificacao proxima a temperatura corporea, ou seja,
no local de tratamento. Todas as formulacoes apresentaram baixos valores de tamanho
de particulas e reducao da polidispersao apos a adicao da teicoplanina, resultando em
formulacoes mais homogeneas. Os fosfatos tricalcicos e a teicoplanina interferiram na
agregacao micelar, alterando a entalpia de formacao de micelas e conferindo alta carga
de superficie negativa, esta conferindo maior estabilidade ao coloide por repulsao
eletrostatica. As formulacoes apresentaram total dissolucao apos 24 horas em contato
com o meio de dissolucao e a liberacao da teicoplanina segue o modelo de Higuchi. As
formulacoes nao sao citotoxicas e sao positivas para a migracao, proliferacao e
diferenciacao celular osteogenica de celulas-tronco de polpa dentaria humana
(hDPSCs). Todas as formulacoes apresentaram alta inibicao do crescimento de cepas
Gram-positivas, principalmente Staphylococcus aureus, principal agente causador da
osteomielite. Os resultados indicaram que as formulacoes a base de poloxamer 407 e
188 (20%:5%, peso/peso) sao promissoras para o carreamento de bioativos, podendo
contribuir para um novo material adequado para o tratamento da osteomielite associada
a regeneracao ossea. / Osteomyelitis is a inflammation of bone very often in several traumas, caused by an
infecting organism. The conventional treatment is the infected bone and adjacente soft
tissue debridement, associated with the systemic administration of antibiotic. This study
characterized the injectable system based in poloxamer 407 (PL407) - alone or in
combination with poloxamer 188 (PL188) - incorporated with the antibiotic teicoplanin
and different compositions of â-TCP (â-TCP) doped with magnesium and/or zinc for
osteomyelitis treatment associated with bone repair. The formulations were
characterized by structural analysis, determination of the sol-gel transition temperature,
evaluation of the in vitro dissolution and teicoplanina release profile, and in vitro
biological characterization. The results showed that the tricalcium phosphate and
teicoplanin did not change the thermal reversibility of poloxamers, but teicoplanin
decreased sol-gel transition temperature. The formulations remained one of the
advantageous features of poloxamer: the ability to be injected in liquid form at room
temperature and near body temperature gelation, in other words, gelation at the
treatment site. All formulations showed lower particle size values and decreased of
polydispersity after addition of teicoplanin, resulting in more homogeneous formulations.
Tricalcium phosphate and teicoplanin interfered in micellar aggregation by changing the
micelle formation enthalpy and confering high load negative surface, this resulting in
more colloid stability by electrostatic repulsion. The formulations showed complete
dissolution after 24 hours in contact with the dissolution medium and teicoplanin release
profile follows the Higuchi model. The formulations are non-cytotoxic and are positive for
cell migration, proliferation and osteogenic differentiation of human dental pulp stem
cells (hDPSCs). All formulations showed high inhibition of the Gram-positive strains
growth, particularly Staphylococcus aureus, the most common organism seen in
osteomyelitis. The results indicated the poloxamer 407 and 188 based formulations
(20%:5%, w/w) are promising to be a bioactive carrier and can contribute to a new
material suitable for the osteomyelitis treatment associated with bone regeneration.
| Identifer | oai:union.ndltd.org:IBICT/oai:BDTD:102715 |
| Date | January 2016 |
| Creators | Kai, Karen Cristina |
| Contributors | Marchi, Juliana, Santos Júnior, Arnaldo Rodrigues dos, Bonvent, Jean Jacques, Rigo, Eliana Cristina da Silva, Marques, Rodrigo Fernando Costa |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf, 128 f. : il. |
| Source | reponame:Repositório Institucional da UFABC, instname:Universidade Federal do ABC, instacron:UFABC |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=102715&midiaext=72868, http://biblioteca.ufabc.edu.br/index.php?codigo_sophia=102715&midiaext=72867, Cover: http://biblioteca.ufabc.edu.brphp/capa.php?obra=102715 |
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