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Mol Pharm ; 17(7): 2287-2298, 2020 07 06.
Article in English | MEDLINE | ID: mdl-32515970

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Helicobacter Infections/microbiology , Helicobacter pylori/drug effects , Helicobacter pylori/physiology , Metal Nanoparticles/chemistry , Polymers/chemistry , Silver Compounds/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Biofilms/drug effects , Cell Line , Drug Delivery Systems/methods , Drug Liberation , Fibroblasts/drug effects , Helicobacter Infections/drug therapy , Humans , Inhibitory Concentration 50 , Larva/drug effects , Lepidoptera/drug effects , Mice , Microbial Sensitivity Tests , Microbial Viability/drug effects , Particle Size , Silver Compounds/chemistry
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