A nanoparticle delivery vehicle for S-nitroso-N-acetyl cysteine: Sustained vascular response

Parimala Nacharaju, Chaim Tuckman-Vernon, Keith E. Maier, Jason Chouake, Adam Friedman, Pedro Cabrales, Joel M. Friedman

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Interest in the development of nitric oxide (NO) based therapeutics has grown exponentially due to its well elucidated and established biological functions. In line with this surge, S-nitroso thiol (RSNO) therapeutics are also receiving more attention in recent years both as potential stable sources of NO as well as for their ability to serve as S-nitrosating agents; S-nitrosation of protein thiols is implicated in many physiological processes. We describe two hydrogel based RSNO containing nanoparticle platforms. In one platform the SNO groups are covalently attached to the particles (SNO-np) and the other contains S-nitroso-N-acetyl cysteine encapsulated within the particles (NAC-SNO-np). Both platforms function as vehicles for sustained activity as trans-S-nitrosating agents. NAC-SNO-np exhibited higher efficiency for generating GSNO from GSH and maintained higher levels of GSNO concentration for longer time (24 h) as compared to SNO-np as well as a previously characterized nitric oxide releasing platform, NO-np (nitric oxide releasing nanoparticles). In vivo, intravenous infusion of the NAC-SNO-np and NO-np resulted in sustained decreases in mean arterial pressure, though NAC-SNO-np induced longer vasodilatory effects as compared to the NO-np. Serum chemistries following infusion demonstrated no toxicity in both treatment groups. Together, these data suggest that the NAC-SNO-np represents a novel means to both study the biologic effects of nitrosothiols and effectively capitalize on its therapeutic potential.

Original languageEnglish (US)
Pages (from-to)150-160
Number of pages11
JournalNitric Oxide - Biology and Chemistry
Volume27
Issue number3
DOIs
StatePublished - Oct 15 2012

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Keywords

  • Nanotechnology
  • Nitric oxide
  • RSNO
  • S-Nitrosoglutathione
  • S-nitroso-N-acetyl-cysteine
  • Vasodilation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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