Journal
MOLECULAR PHARMACEUTICS
Volume 16, Issue 7, Pages 2912-2921Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00110
Keywords
nitric oxide delivery; silica nanoparticles; cyanide trapping; vasodilation; cytotoxicity
Funding
- CNPq [306896/2018-4, 308383/2018-4, 303355/2018-2]
- PRONEX [PR2 0101-00030.01.00/15]
- CAPES [23038.008968/2012-87, PROEX 23038.000936/2018-46]
- FUNCAP
- CAPES (CAPES/Print/UFC)
- [403866/2016-2]
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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 (zeta = 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 mu mol 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 mu M), while SNP exhibited an LC50 of 228 mu 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.
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