Incorporation of Nitroprusside on Silica Nanoparticles—A Strategy for Safer Use of This NO Donor in Therapy

Abstract

Silica-based nanoparticles have been developed as powerful platforms for drug delivery and might also prevent undesired side effects of drugs. Here, a fast method to synthesize positively charged mesoporous silica nanoparticles (ζ = 20 ± 0.5 mV, surface area = 678 m 2 g −1 , and 2.3 nm of porous size) was reported. This nanomaterial was employed to anchor sodium nitroprusside (SNP), a vasodilator drug with undesired cyanide release. A remarkable incorporation of 323.9 ± 7.55 μmol of SNP per gram of nanoparticle was achieved, and a series of studies of NO release were conducted, showing efficient release of NO along with major cyanide retention (ca. 64% bound to nanoparticle). Biological assays with mammalian cells showed only a slight drop in cell viability (13%) at the highest concentration (1000 μM), while SNP exhibited an LC 50 of 228 μM. Moreover, pharmacological studies demonstrated similar efficacy for vasodilation and sGC-PKG-VASP pathway activation when compared to SNP alone. Altogether, this new SNP silica nanoparticle has great potential as an alternative for wider and safer use of SNP in medicine with lower cyanide toxicity.

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

“…Most of these nanoparticles showed that SNP was released by measuring free iron, ,, which can be misleading. Three nanomaterials showed evidence of NO release either by using a direct NO sensor , or indirectly measuring its decomposition product (nitrite) . Interestingly, there is only one nanomaterial that researchers measured cyanide release and even showed it was mainly trapped by the nanoparticle .…”

“…Drug delivery and potential nitroprusside carriers: (i) TEM images of nanoparticles of MNP-SNP illustrate their sizes and porosity enabling expressive drug binding; (ii) it illustrates a proposal of how cyanide release was reduced by nanocarrier’s nature (e.g., cyanide adsorption on the positively charged surface of the carrier); (iii) therapeutic effects versus conventional (black ---) and controlled-release drug administration (red ---); and (iv) possible curtail of leaching losses on topical administration of this nanomaterial.…”

“…NO is involved in a myriad of processes in humans, including modulation of blood pressure and flow, tubular organ compliance, platelet aggregation, cell defense, memory, and blood vessel angiogenesis, among others. In bacteria, NO has been associated with the regulation of biofilm formation, quorum sensing, and also counter-defense to host. , Consequently, the therapeutic potential of NO donor molecules has bloomed with many exciting products in use and others under development. − Indeed, there are many old and new applications for NO donors such as antiparasitic, antihypertensive, anti-inflammatory pain, glaucoma, − asthma, arthritis, sexual impotence, bacterial biofilm disruption, , wound healing, , and anti-COVID-19, among many others. − Besides that, some companies (e.g., Bellerophon, Vero Biotech, BeyondAir) have also developed devices to generate NO in situ , which might be useful for certain conditions, despite that they still bear limitations of dosing, cost, and discomfort on their use.…”

Pentacyanoferrate(II) complex of pyridine-4- and pyrazine-2-hydroxamic acid as source of HNO: investigation of anti-tubercular and vasodilation activities

“…Again, the ligand 2 and 5 and the complex 6 were also tested for comparison. The NO species is indeed known to induce vasodilation of blood vessels, and NO carrier molecules, such as sodium nitroprusside (SNP, Na 2 [Fe II (CN) 5 (NO)), have an important therapeutic effect for hypertensive crises [40]. At the same time, HNO, the reduced and protonated form of NO .…”

Nitric oxide donor andrographolide enhances humoral and cell-mediated immune responses

“…Nitric oxide (NO) is an important messenger molecule which has a wide range of physiological functions. In vivo, nitroglycerin, sodium nitroprusside (SNP) and other NO donors release high amount of NO capable of inducing apoptosis in tumor cells (14,15). In a previous study, the secretion of IFN-γ by spleen cells in mice treated with andrographolide was significantly increased relative to the control, suggesting that andrographolide increases the specificity of cellular immunity (9,16).…”