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Master's Dissertation
DOI
https://doi.org/10.11606/D.23.2020.tde-24022021-182716
Document
Author
Full name
Priscila Lucena Mendes
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Adde, Carlos Alberto (President)
Rovai, Emanuel da Silva
Sipert, Carla Renata
Veloso, Danillo Fabrini Maciel Costa
Title in Portuguese
Efeito de nanoparticulas carreadas com sinvastatina na viabilidade e diferenciação osteogênica de células-tronco do ligamento periodontal
Keywords in Portuguese
Células-tronco
Ligamento periodontal
Nanopartículas poliméricas
Regeneração tecidual
Sinvastatina
Abstract in Portuguese
O uso de polímeros como nanocarreadores de fármacos oferece flexibilidade na dosagem e na cinética de liberação, melhorando a eficácia dos tratamentos. A sinvastatina, medicamento utilizado para a redução do colesterol tem demonstrado ação na estimulação da formação óssea. Acredita-se que este efeito pleiotrópico, associado à possibilidade de obtenção de um sistema de liberação controlada pode levar a um aumento na osteogênese. No presente estudo, investigamos os efeitos das nanopartículas carregadas com sinvastatina na viabilidade e diferenciação de PDLSCs, in vitro, quando cultivadas em meio indutor específico. As culturas foram divididas nos seguintes grupos: 1) PDLSC em meio clonogênico (C); 2) PDLSC em meio clonogênico com dimetilsufóxido (C+D); 3) PDLSC em meio clonogênico com dimetilsufóxido e sinvastatina (S); 4) PDLSC em meio osteogênico (MO); 5) Grupo nanopartícula branca (NB): PDLSC receberam a formulação de nanopartículas sem sinvastatina em meio osteogênico; 6) Grupo nanopartículas carreadas com sinvastatina (NS): PDLSC receberam a formulação da sinvastatina encapsulada em nanopartículas poliméricas de PDLLA em meio osteogênico. As concentrações de 103?M, 10-2?M foram selecionadas após o ensaio de proliferação. A avaliação da mineralização por deposição de cálcio foi realizada através da coloração com vermelho de alizarina. Diante dos dados obtidos nesse trabalho, é possível concluir que as nanopartículas de PDLLA podem atuar como veiculo para a entrega contínua e gradual da sinvastatina. As nanopartículas carreadas com 10-2 µM de sinvastatina não apresentaram citotoxicidade e aumentaram de forma significativa a atividade celular. As nanopartículas de PDLLA carregadas com sinvastatina causaram um aumento no depósito de cálcio, sugerindo que esse pode ser um biomaterial promissor para osteoindução in vivo, reiterando o potencial osteogênico da sinvastina. Novos estudos são necessários a fim de se verificar a melhora dos parâmetros ósseos in vivo.
Title in English
The effect of nanoparticles loaded with simvastatin on viability and osteogenic differentiation in periodontal ligament stem cell cultures
Keywords in English
Periodontal ligament
Polymeric nanoparticles
Simvastatin
Stem cells
Tissue Regeneration
Abstract in English
The use of polymers as drug nanocarriers offers flexibility in dosage and release kinetics, improving the effectiveness of treatments. Simvastatin, a drug used to reduce cholesterol has been shown to stimulate bone formation. It is supposed that this pleiotropic effect, associated with the possibility of using a controlled release system, can cause an increase in osteogenesis. In the current study, we investigated the effects of nanoparticles loaded with simvastatin on the viability and differentiation of PDLSCs, in vitro, when grown in a specific inducing medium. As cultures, they were divided into the following groups: 1) PDLSC in clonogenic medium (C); 2) PDLSC in a clonogenic medium with dimethylsulfoxide (C + D); 3) PDLSC in a clonogenic medium with dimethylsulfoxide and simvastatin (S); 4) PDLSC in osteogenic medium (MO); 5) White nanoparticle group (NB): PDLSC received the application of nanoparticles without simvastatin in the osteogenic medium; 6) Nanoparticles group loaded with simvastatin (NS): PDLSC received the application of simvastatin encapsulated in polymeric nanoparticles of PDLLA in osteogenic medium. As 10-3?M, 10-2?M were selected after the proliferation test. An assessment of mineralization by calcium deposition was performed by staining with alizarin red. Given the data selected in this work, it is possible to conclude that PDLLA nanoparticles can perform as a vehicle for continuous and gradual delivery of simvastatin. As nanoparticles carried with 10-2 µM of simvastatin, no cytotoxicity was found and significantly increased cell activity. As simvastatin-loaded PDLLA nanoparticles cause an increase in calcium deposits, suggesting that this may be a biomaterial promoter for osteoinduction in vivo, reiterating the osteogenic potential of simvastin. Further studies are needed to verify improvements in bone parameters in vivo.
 
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Publishing Date
2021-02-26
 
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