Activity of poly(methacrylic acid)-silver nanoparticles on fluconazole-resistant Candida albicans strains: Synergistic and cytotoxic effects.

AIMS: To synthesize and evaluate the antifungal activity of poly(methacrylic acid)-silver nanoparticles (PMAA-AgNPs) against nine Candida albicans isolated from clinical specimens. METHODS AND RESULTS: The effects of PMAA-AgNPs-fluconazole combination was analysed by checkerboard methodology. The synergistic potential of PMAA-AgNPs-fluconazole was determined by the fractional inhibitory concentration index (FICI). The inhibition of germ tube formation and the determination of PMAA-AgNPs cytotoxicity were also performed. All C. albicans strains were susceptible to PMAA-AgNPs and resistant to fluconazole. PMAA-AgNPs at subinhibitory concentrations restored the susceptibility of resistant C. albicans to fluconazole, whose FICI ranged from 0.3 to 0.5. The synergistic interaction of the combination was observed in eight of nine strains. The PMAA-AgNPs-fluconazole combination was also able to inhibit the germ tube formation. PMAA-AgNPs showed a dose-dependent decrease in viability for cells tested, with 50% cytotoxic concentration (CC50 ) values of 6.5, 4.9 and 6.8 µg ml-1 for macrophages, fibroblasts and Vero cells, respectively. CONCLUSIONS: This study demonstrated that, in general, PMAA-AgNPs acts synergistically in combination with fluconazole, inhibiting fluconazole-resistant C. albicans strains. PMAA-AgNPs-fluconazole combination was also able to inhibit germ tube formation, an important virulence factor. Inhibitory effect of PMAA-AgNPs alone or in combination was higher in C. albicans than in mammalian cells. SIGNIFICANCE AND IMPACT OF STUDY: This study shows the potential of PMAA-AgNPs combined with fluconazole to inhibit fluconazole-resistant C. albicans strains.

Peptides for Coating TiO2 Implants: An In Silico Approach.

Titanium is usually used in the manufacturing of metal implants due to its biocompatibility and high resistance to corrosion. A structural and functional connection between the living bone and the surface of the implant, a process called osseointegration, is mandatory for avoiding prolonged healing, infections, and tissue loss. Therefore, osseointegration is crucial for the success of the implantation procedure. Osseointegration is a process mediated by bone-matrix progenitor cells' proteins, named integrins. In this study, we used an in silico approach to assemble and test peptides that can be strategically used in sensitizing TiO2 implants in order to improve osseointegration. To do so, we downloaded PDB structures of integrins α5ß1, αvß3, and αIIbß3; their biological ligands; and low-cost proteins from the Protein Data Bank, and then we performed a primary (integrin-protein) docking analysis. Furthermore, we modeled complex peptides with the potential to bind to the TiO2 surface on the implant, as well as integrins in the bone-matrix progenitor cells. Then we performed a secondary (integrin-peptide) docking analysis. The ten most promising integrin-peptide docking results were further verified by molecular dynamics (MD) simulations. We recognized 82 peptides with great potential to bind the integrins, and therefore to be used in coating TiO2 implants. Among them, peptides 1 (GHTHYHAVRTQTTGR), 3 (RKLPDATGR), and 8 (GHTHYHAVRTQTLKA) showed the highest binding stability during the MD simulations. This bioinformatics approach saves time and more effectively directs in vitro studies.

Titanium Dental Implants: An Overview of Applied Nanobiotechnology to Improve Biocompatibility and Prevent Infections.

This review addresses the different aspects of the use of titanium and its alloys in the production of dental implants, the most common causes of implant failures and the development of improved surfaces capable of stimulating osseointegration and guaranteeing the long-term success of dental implants. Titanium is the main material for the development of dental implants; despite this, different surface modifications are studied aiming to improve the osseointegration process. Nanoscale modifications and the bioactivation of surfaces with biological molecules can promote faster healing when compared to smooth surfaces. Recent studies have also pointed out that gradual changes in the implant, based on the microenvironment of insertion, are factors that may improve the integration of the implant with soft and bone tissues, preventing infections and osseointegration failures. In this context, the understanding that nanobiotechnological surface modifications in titanium dental implants improve the osseointegration process arouses interest in the development of new strategies, which is a highly relevant factor in the production of improved dental materials.

Nanopartículas de prata em bases de próteses de PMMA para controle de atividade microbiana / Silver nanoparticles in PMMA prosthesis bases to control microbial activity

Objetivo:Avaliar in vitro a atividade de Staphylococcus aureus e Candida albicans em bases de próteses convencionais à base de polimetilmetacrilato de metila com nanopartículas de prata incorporadas a sua composição. Métodos: Foi realizado um estudo experimental laboratorial com resinas acrílicas autopolimerizáveis comercialmente disponíveis, Vipi Flash/VIPI e JET/Clássico. Foram confeccionados 80 corpos de prova, divididos em 16 grupos (n = 5), referentes ao tipo de resina, tratamento (incorporação e imersão na solução de nanopartículas de prata) e microrganismo inoculado. As nanopartículas foram sintetizadas com ácido polimetacrílico, nitrato de prata e irradiadas com luz ultravioleta de baixa potência (~8W) por 6 horas, e as suas concentrações idealizadas pelo método de microdiluição em placas para determinação da concentração mínima inibitória frente aos microrganismos selecionados. Verificou-se ação bactericida e fungicida com concentração inicial de 25% e após fator de diluição 12,5%. Resultados: Houve dificuldade de incorporação das nanopartículas na resina acrílica, que pode decorrer da alteração da proporção 3:1 recomendada pelo fabricante ou pela redução ou inativação da ação da nanopartícula de prata pela interação com o polimetilmetacrilato. VIPI com inclusão de nanopartícula obteve menor aderência de biofilme de Candida albicans. Conclusão:A nanopartícula de prata mostrou-se eficaz na sua ação de controle de Candida albicans e Staphylococcus aureus no método de imersão, entretanto, a sua ação antimicrobiana foi comprometida após inclusão nas resinas acrílicas.

Aim:To perform an in vitro evaluation of the activity of Staphylococcus aureus and Candida albicansin conventional prosthesis bases, based on methyl polymethylmethacrylate with silver nanoparticles incorporated into the composition. Methods: An experimental laboratory study was carried out using commercially available self-curing acrylic resins, Vipi Flash/VIPI and JET/Clássico. Eighty specimens were manufactured and divided into 16 groups (n = 5), referent to the resin brand, treatment (incorporation and immersion in the silver nanoparticle solution), and inoculated microorganism. The nanoparticles were synthesized with polymethacrylic acid and silver nitrate, and were irradiated with a low power (~ 8W) ultraviolet light for 6 hours. Their concentrations were idealized by the method of microplate dilution to determine the minimum inhibitory concentration when compared to the selected microorganisms. Bactericidal and fungicidal activities were identified with an initial concentration of 25% and a subsequent dilution factor of 12.5%. Results:It was difficult to incorporate the AgNPs into the acrylic resin, which may well have resulted from the change from the 3:1 proportion recommended by the manufacturer or by reducing or inactivating the action of the silver nanoparticle by interaction with polymethylmethacrylate. VIPI with the inclusion of nanoparticles obtained a lesser Candida albicans biofilm adherence. Conclusion: Silver nanoparticles were effective in controlling Candida albicans and Staphylococcus aureus in the immersion method; however, the antimicrobial activity was compromised after inclusion in acrylic resins.