A Nanoparticle Delivery Vehicle for S-nitroso-N-acetyl Cysteine: Sustained Vascular Response

Overview

Journal Nitric Oxide

Publisher Elsevier

Date 2012 Jun 19

PMID 22705913

Citations 17

Authors

Parimala Nacharaju

Chaim Tuckman-Vernon

Keith E Maier

Jason Chouake

Adam Friedman

Pedro Cabrales

Joel M Friedman

Affiliations

Soon will be listed here.

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.

Citing Articles

Nitric oxide-loaded nano- and microparticle platforms serving as potential new antifungal therapeutics.

Liu S, Zamith-Miranda D, Almeida-Paes R, da Silva L, Nacharaju P, Nosanchuk J Fungal Biol. 2023; 127(7-8):1224-1230.

PMID: 37495312 PMC: 10372338. DOI: 10.1016/j.funbio.2023.01.007.

Nanotechnology as a tool to advance research and treatment of non-oncologic urogenital diseases.

Loloi J, Babar M, Davies K, Suadicani S Ther Adv Urol. 2022; 14:17562872221109023.

PMID: 35924206 PMC: 9340423. DOI: 10.1177/17562872221109023.

Recent Advances in Hydrogel-Mediated Nitric Oxide Delivery Systems Targeted for Wound Healing Applications.

Tavares G, Alves P, Simoes P Pharmaceutics. 2022; 14(7).

PMID: 35890273 PMC: 9315818. DOI: 10.3390/pharmaceutics14071377.

The Application of Nitric Oxide for Ocular Hypertension Treatment.

Han B, Song M, Li L, Sun X, Lei Y Molecules. 2021; 26(23).

PMID: 34885889 PMC: 8659272. DOI: 10.3390/molecules26237306.

Control of systemic inflammation through early nitric oxide supplementation with nitric oxide releasing nanoparticles.

Williams A, Muller C, Govender K, Navati M, Friedman A, Friedman J Free Radic Biol Med. 2020; 161:15-22.

PMID: 33011274 PMC: 7529593. DOI: 10.1016/j.freeradbiomed.2020.09.025.

References

Slivka A, Chuttani R, Carr-Locke D, Kobzik L, Bredt D, Loscalzo J . Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans. J Clin Invest. 1994; 94(5):1792-8. PMC: 294570. DOI: 10.1172/JCI117527. View

Tsui D, Gambino A, Wanstall J . S-nitrosocaptopril: acute in-vivo pulmonary vasodepressor effects in pulmonary hypertensive rats. J Pharm Pharmacol. 2003; 55(8):1121-5. DOI: 10.1211/0022357021369. View

Priora R, Margaritis A, Frosali S, Coppo L, Summa D, Di Giuseppe D . In vitro inhibition of human and rat platelets by NO donors, nitrosoglutathione, sodium nitroprusside and SIN-1, through activation of cGMP-independent pathways. Pharmacol Res. 2011; 64(3):289-97. DOI: 10.1016/j.phrs.2011.03.014. View

Foster M, McMahon T, Stamler J . S-nitrosylation in health and disease. Trends Mol Med. 2003; 9(4):160-8. DOI: 10.1016/s1471-4914(03)00028-5. View

Maragos C, Morley D, Wink D, Dunams T, Saavedra J, Hoffman A . Complexes of .NO with nucleophiles as agents for the controlled biological release of nitric oxide. Vasorelaxant effects. J Med Chem. 1991; 34(11):3242-7. DOI: 10.1021/jm00115a013. View

Brune B, Mohr S, Messmer U . Protein thiol modification and apoptotic cell death as cGMP-independent nitric oxide (NO) signaling pathways. Rev Physiol Biochem Pharmacol. 1996; 127:1-30. DOI: 10.1007/BFb0048263. View

Grossi L, Montevecchi P . A kinetic study of S-nitrosothiol decomposition. Chemistry. 2002; 8(2):380-7. DOI: 10.1002/1521-3765(20020118)8:2<380::AID-CHEM380>3.0.CO;2-P. View

Stamler J, Simon D, Osborne J, Mullins M, Jaraki O, Michel T . S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci U S A. 1992; 89(1):444-8. PMC: 48254. DOI: 10.1073/pnas.89.1.444. View

Hibbs Jr J, Taintor R, Vavrin Z, Rachlin E . Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988; 157(1):87-94. DOI: 10.1016/s0006-291x(88)80015-9. View

10.

Ahern G, Klyachko V, Jackson M . cGMP and S-nitrosylation: two routes for modulation of neuronal excitability by NO. Trends Neurosci. 2002; 25(10):510-7. DOI: 10.1016/s0166-2236(02)02254-3. View

11.

Stuehr D, Gross S, Sakuma I, Levi R, Nathan C . Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide. J Exp Med. 1989; 169(3):1011-20. PMC: 2189276. DOI: 10.1084/jem.169.3.1011. View

12.

Cabrales P, Han G, Roche C, Nacharaju P, Friedman A, Friedman J . Sustained release nitric oxide from long-lived circulating nanoparticles. Free Radic Biol Med. 2010; 49(4):530-8. PMC: 2903640. DOI: 10.1016/j.freeradbiomed.2010.04.034. View

13.

Marletta M, Yoon P, Iyengar R, Leaf C, Wishnok J . Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988; 27(24):8706-11. DOI: 10.1021/bi00424a003. View

14.

Martinez L, Han G, Chacko M, Mihu M, Jacobson M, Gialanella P . Antimicrobial and healing efficacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infection. J Invest Dermatol. 2009; 129(10):2463-9. DOI: 10.1038/jid.2009.95. View

15.

Jaffrey S, Snyder S . Nitric oxide: a neural messenger. Annu Rev Cell Dev Biol. 1995; 11:417-40. DOI: 10.1146/annurev.cb.11.110195.002221. View

16.

Hogg N . The biochemistry and physiology of S-nitrosothiols. Annu Rev Pharmacol Toxicol. 2002; 42:585-600. DOI: 10.1146/annurev.pharmtox.42.092501.104328. View

17.

McDonald L, Murad F . Nitric oxide and cyclic GMP signaling. Proc Soc Exp Biol Med. 1996; 211(1):1-6. DOI: 10.3181/00379727-211-43950a. View

18.

Friedman A, Blecher K, Schairer D, Tuckman-Vernon C, Nacharaju P, Sanchez D . Improved antimicrobial efficacy with nitric oxide releasing nanoparticle generated S-nitrosoglutathione. Nitric Oxide. 2011; 25(4):381-6. DOI: 10.1016/j.niox.2011.09.001. View

19.

Bates J, Baker M, Guerra Jr R, Harrison D . Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required. Biochem Pharmacol. 1991; 42 Suppl:S157-65. DOI: 10.1016/0006-2952(91)90406-u. View

20.

Friedman A, Han G, Navati M, Chacko M, Gunther L, Alfieri A . Sustained release nitric oxide releasing nanoparticles: characterization of a novel delivery platform based on nitrite containing hydrogel/glass composites. Nitric Oxide. 2008; 19(1):12-20. DOI: 10.1016/j.niox.2008.04.003. View