Nanoplataforma de Sílica Mesoporosa liberadora de Óxido Nítrico e suas Potenciais Aplicações Terapêuticas

• Ano de defesa: 2022
• Autor(a) principal: Silva Filho, Pedro Martins da
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Nanopartículas; Sílica; Aplicação terapêutica; Óxido nítrico
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/66231

The development of nanoplatforms containing NO-releasing molecules emerged as a strategy to reduce toxic effects, improving safety and therapeutic efficiency of the molecule. Furthermore, for therapeutic applications, dosage control is extremely important, which requires an efficient releasing method. Mesoporous silica (MPSi) based nanoplatforms have shown themselves to be an interesting host for many molecules and biomolecules. These materials are easily functionalized, which improves their biocompatibility, offering a versatile platform to the incorporation of NO donors such as sodium nitroprusside (SNP). Sodium nitroprusside is a potent nitric oxide (NO) releaser, although of limited use due to its cyanide emission. Previous studies have shown that MPSi present high adsorption of sodium nitroprusside, about 323,9 ± 7,6 μmol g−1, and this platform was named MPSi-NP. In the current work the MPSi-NP were used in different therapeutical treatments. Cytotoxicity tests showed an excellent reduction in cyanide release (64%) and biological tests, with mammalian cells, showed only a slight drop in cell viability (13%) for the 1000 μM concentration, while SNP showed a CL50 of 228 μmol L˗1. MPSi-NP presented similar efficacy to vasodilation and activation via sGC-PKG-VASP when compared to free SNP. Dialysis assays using ambient light and 37ºC temperature showed that MPSi-NP released 63% of NO in contrast with only 18% of SNP during the first 24 hours, which indicates that silica acts as NO release facilitator. For antibacterial activity, the SNP presented moderated antibiofilm activity and the MPSi-NP were capable of reducing the viable cells of biofilm to resistant bacteria in 641 times for Staphylococcus aureus ATCC 700698 and 1445 times for Staphylococcus epidermidis ATCC 35984. MPSi-NP was able to reduce ampicillin’s CIM by half for S. aureus ATCC 00698 and four times for S. epidermidis ATCC 35984. Formulations with MPSi-NP, a gel (gel-MPSi-NP) and cotton fiber with the MPSi-NP (cotton-MPSi-NP) showed NO release. All this shows the potential for topical application of MPSi-NP as antinociceptive, anti-inflammatory, antibacterial.