Document Detail

Sustained release nitric oxide from long-lived circulating nanoparticles.
MedLine Citation:
PMID:  20460149     Owner:  NLM     Status:  MEDLINE    
The current limitations of nitric oxide (NO) delivery systems have stimulated an extraordinary interest in the development of compounds that generate NO in a controlled and sustained manner with a heavy emphasis on the treatment of cardiovascular disease states. This work describes the positive physiological response to the infusion of NO-releasing nanoparticles prepared using a new platform based on hydrogel/glass hybrid nanoparticles. When exposed to moisture, these nanoparticles slowly release therapeutic levels of NO, previously generated through thermal reduction of nitrite to NO trapped within the dry particles. The controlled and sustained release of NO observed from these nanoparticles (NO-np) is regulated by its hydration over extended periods of time. In a dose-dependent manner, circulating NO-np both decreased mean arterial blood pressure and increased exhaled concentrations of NO over a period of several hours. Circulating NO-np induced vasodilatation and increased microvascular perfusion during their several hour circulation lifetime. Control nanoparticles (control-np; without nitrite) did not induce changes in arterial pressure, although a decrease in the number of capillaries perfused and an increase in leukocyte rolling and immobilization in the microcirculation were observed. The NO released by the NO-np prevents the inflammatory response observed after infusion of control-np. These data suggest that NO release from NO-np is advantageous relative to other NO-releasing compounds, because it does not depend on chemical decomposition or enzymatic catalysis; it is only determined by the rate of hydration. Based on the observed physiological properties, NO-np has clear potential as a therapeutic agent and as a research tool to increase our understanding of NO signaling mechanisms within the vasculature.
Pedro Cabrales; George Han; Camille Roche; Parimala Nacharaju; Adam J Friedman; Joel M Friedman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-05-09
Journal Detail:
Title:  Free radical biology & medicine     Volume:  49     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-13     Completed Date:  2011-01-21     Revised Date:  2014-06-02    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  530-8     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Delayed-Action Preparations
Drug Delivery Systems*
Hydrogel / chemistry
Hydrogen-Ion Concentration
Nanoparticles / chemistry*
Nanotechnology / instrumentation,  methods
Nitric Oxide / administration & dosage*,  chemistry*,  metabolism,  pharmacokinetics
Particle Size
Signal Transduction
Grant Support
Reg. No./Substance:
0/Delayed-Action Preparations; 25852-47-5/Hydrogel; 31C4KY9ESH/Nitric Oxide
Comment In:
Free Radic Biol Med. 2010 Aug 15;49(4):528-9   [PMID:  20639121 ]

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