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Mol Pharm ; 17(7): 2287-2298, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32515970

RESUMO

Helicobacter pylori inhabits the gastric epithelium and can promote the development of gastric disorders, such as peptic ulcers, acute and chronic gastritis, mucosal lymphoid tissue (MALT), and gastric adenocarcinomas. To use nanotechnology as a tool to increase the antibacterial activity of silver I [Ag(I)] compounds, this study suggests a new strategy for H. pylori infections, which have hitherto been difficult to control. [Ag (PhTSC·HCl)2] (NO3)·H2O (compound 1) was synthesized, characterized, and loaded into polymeric nanoparticles (PN1). PN1 had been developed by nanoprecipitation with poly(ε-caprolactone) polymer and poloxamer 407 surfactant. System characterization assays showed that the PNs had adequate particle sizes and ζ-potentials. Transmission electron microscopy confirmed the formation of polymeric nanoparticles (PNs). Compound 1 had a minimum inhibitory concentration for H. pylori of 3.90 µg/mL, which was potentiated to 0.781 µg/mL after loading. The minimum bactericidal concentration of 7.81 µg/mL was potentiated 5-fold to 1.56 µg/mL in PN. Compound 1 loaded in PN1 displayed better activity for H. pylori biofilm formation and mature biofilm. PN1 reduced the toxicity of compound 1 to MRC-5 cells. Loading compound 1 into PN1 inhibited the mutagenicity of the free compound. In vivo, the system allowed survival of Galleria mellonella larvae at a concentration of 200 µg/mL. This is the first demonstration of the antibacterial activity of a silver complex enclosed in polymeric nanoparticles against H. pylori.


Assuntos
Antibacterianos/farmacologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/fisiologia , Nanopartículas Metálicas/química , Polímeros/química , Compostos de Prata/farmacologia , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Fibroblastos/efeitos dos fármacos , Infecções por Helicobacter/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Larva/efeitos dos fármacos , Lepidópteros/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Tamanho da Partícula , Compostos de Prata/química
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