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

Mol Pharm. 2019 Jul 1;16(7):2912-2921. doi: 10.1021/acs.molpharmaceut.9b00110. Epub 2019 May 24.

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 m2 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 LC50 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.

Keywords: cyanide trapping; cytotoxicity; nitric oxide delivery; silica nanoparticles; vasodilation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Guinea Pigs
  • Male
  • Nanoparticles / chemistry*
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / adverse effects*
  • Nitric Oxide Donors / chemistry*
  • Nitroprusside / adverse effects*
  • Nitroprusside / chemistry*
  • Porosity
  • Pulmonary Artery / drug effects
  • Rats
  • Rats, Wistar
  • Silicon Dioxide / chemistry*
  • Surface Properties
  • Vero Cells

Substances

  • Nitric Oxide Donors
  • Nitroprusside
  • Nitric Oxide
  • Silicon Dioxide