The biofilm inhibition activity of a NO donor nanosilica with enhanced antibiotics action

• Published in: International journal of pharmaceutics Vol. 610; p. 121220
• Main Authors: da Silva Filho, Pedro Martins, Andrade, Alexandre Lopes, Lopes, Jessica Barros Arrais Cruz, Pinheiro, Aryane de Azevedo, de Vasconcelos, Mayron Alves, Fonseca, Said Gonçalves da Cruz, Lopes, Luiz Gonzaga de França, Sousa, Eduardo Henrique Silva, Teixeira, Edson Holanda, Longhinotti, Elisane
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2021
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Biofilm; Biofilms; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nitric Oxide Donors - pharmacology; Nitroprusside; Renal Dialysis; Resistance; Silica nanoparticles; Staphylococcal Infections; Staphylococcus aureus; Resistance; Nitroprusside; Silica nanoparticles; Biofilm; Antibiotics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.121220

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•MPSi-NP presents high speed of NO dialysis.•MPSi-NP acts on the inhibition of Staphylococcus biofilm.•MPSi-NP and ampicillin against S. epidermidis ATCC 35,984 have synergistic action.•MPSi-NP have low toxicity compared to other silica materials.
Nitric oxide (NO) has emerged as a promising antibacterial agent, where NO donor compounds have been explored. Here, we investigated the role of a silica nanoparticle containing nitroprusside (MPSi-NP) as a NO donor agent against methicillin-sensitive (ATCC 25,923 and ATCC 12228) and methicillin-resistant (ATCC 700,698 and ATCC 35984) Staphylococcus strains. Biofilm inhibition was studied along with antibiotic activity in combination with standard antibiotics (ampicillin and tetracycline). MPSi-NP exhibited thermal release of 63% of NO within 24 h, while free nitroprusside released only 18% during a dialysis assay, indicating an assisted release of NO mediated by the nanoparticles. This nanomaterial showed only a moderate activity in blocking biofilm production, but exhibited a significant decrease in the number of viable bacterial cells (over 600-fold for Staphylococcus aureus ATCC 700,698 and Staphylococcus epidermidis ATCC 35984). Remarkably, even using MPSi-NP at concentrations below any antibacterial action, its combination with ampicillin promoted a significant decrease in MIC for resistant strains of S. aureus ATCC 700,698 (2-fold) and S. epidermidis ATCC 35,984 (4-fold). A carbopol-based gel formulation with MPSi-NP (0.5% w/w) was prepared and showed a zone of inhibition of 7.7 ± 0.6 mm for S. epidermidis ATCC 35984. Topical use of MPSi-NP in combination with antibiotics might be a manageable strategy to prevent and eventually treat complicated resistant bacterial infections.