Nitroprusside─Expanding the Potential Use of an Old Drug Using Nanoparticles.

For more than 70 years, sodium nitroprusside (SNP) has been used to treat severe hypertension in hospital emergency settings. During this time, a few other clinical uses have also emerged such as in the treatment of acute heart failure as well as improving mitral incompetence and in the intra- and perioperative management during heart surgery. This drug functions by releasing nitric oxide (NO), which modulates several biological processes with many potential therapeutic applications. However, this small molecule has a short lifetime, and it has been administered through the use of NO donor molecules such as SNP. On the other hand, SNP also has some setbacks such as the release of cyanide ions, high water solubility, and very fast NO release kinetics. Currently, there are many drug delivery strategies that can be applied to overcome many of these limitations, providing novel opportunities for the use of old drugs, including SNP. This Perspective describes some nitroprusside properties and highlights new potential therapeutic uses arising from the use of drug delivery systems, mainly silica-based nanoparticles. There is a series of great opportunities to further explore SNP in many medical issues as reviewed, which deserves a closer look by the scientific community.

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

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.