Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)

Frank C Barone,1 Cezary Marcinkiewicz,2,3 Jie Li,1 Mark Sternberg,3 Peter I Lelkes,2 Dmitriy A Dikin,4 Peter J Bergold,1 Jonathan A Gerstenhaber,2 Giora Feuerstein3 1Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA; 2Department of Bioengineering, Temple University, College...

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Autores principales:	Barone FC, Marcinkiewicz C, Li J, Sternberg M, Lelkes PI, Dikin DA, Bergold PJ, Gerstenhaber JA, Feuerstein G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Fluorescent Nanodiamond Particles Bio-compatibility Near Infra-Red imaging Scanning Electron Microscopy Neurobehavioral Function Pharmacokinetics Rat Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/368eac231e1240f3b4032b4f521876f5
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spelling	oai:doaj.org-article:368eac231e1240f3b4032b4f521876f52021-12-02T02:14:23ZPilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)1178-2013https://doaj.org/article/368eac231e1240f3b4032b4f521876f52018-09-01T00:00:00Zhttps://www.dovepress.com/pilot-study-on-biocompatibility-of-fluorescent-nanodiamond-nv-z800-par-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Frank C Barone,1 Cezary Marcinkiewicz,2,3 Jie Li,1 Mark Sternberg,3 Peter I Lelkes,2 Dmitriy A Dikin,4 Peter J Bergold,1 Jonathan A Gerstenhaber,2 Giora Feuerstein3 1Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA; 2Department of Bioengineering, Temple University, College of Engineering, Philadelphia, PA, USA; 3Debina Diagnostics Inc, Newtown Square, PA, USA; 4Department of Mechanical Engineering, Temple University, Philadelphia, PA, USA Introduction: We hereby report on studies aimed to characterize safety, pharmacokinetics, and bio-distribution of fluorescent nanodiamond particles (NV)-Z~800 (FNDP-(NV)) administered to rats by intravenous infusion in a single high dose. Methods: Broad scale biological variables were monitored following acute (90 minutes) and subacute (5 or 14 days) exposure to FNDP-(NV). Primary endpoints included morbidity and mortality, while secondary endpoints focused on hematology and clinical biochemistry biomarkers. Particle distribution (liver, spleen, lung, heart, and kidney) was assessed by whole organ near infrared imaging using an in vivo imaging system. This was validated by the quantification of particles extracted from the same organs and visualized by fluorescent and scanning electron microscopy. FNDP-(NV)-treated rats showed no change in morbidity or mortality and preserved normal motor and sensory function, as assessed by six different tests. Results: Blood cell counts and plasma biochemistry remained normal. The particles were principally distributed in the liver and spleen. The liver particle load accounted for 51%, 24%, and 18% at 90 minutes, 5 days, and 14 days, respectively. A pilot study of particle clearance from blood indicated 50% clearance 33 minutes following the end of particle infusion. Conclusion: We concluded that systemic exposure of rats to a single high dose of FDNP-(NV)-Z~800 (60 mg/kg) appeared to be safe and well tolerated over at least 2 weeks. These data suggest that FNDP-(NV) should proceed to preclinical development in the near future. Keywords: fluorescent nanodiamond particles, biocompatibility, near infrared imaging, scanning electron microscopy, neurobehavioral function, pharmacokinetics, ratBarone FCMarcinkiewicz CLi JSternberg MLelkes PIDikin DABergold PJGerstenhaber JAFeuerstein GDove Medical PressarticleFluorescent Nanodiamond ParticlesBio-compatibilityNear Infra-Red imagingScanning Electron MicroscopyNeurobehavioral FunctionPharmacokineticsRatMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5449-5468 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fluorescent Nanodiamond Particles Bio-compatibility Near Infra-Red imaging Scanning Electron Microscopy Neurobehavioral Function Pharmacokinetics Rat Medicine (General) R5-920
spellingShingle	Fluorescent Nanodiamond Particles Bio-compatibility Near Infra-Red imaging Scanning Electron Microscopy Neurobehavioral Function Pharmacokinetics Rat Medicine (General) R5-920 Barone FC Marcinkiewicz C Li J Sternberg M Lelkes PI Dikin DA Bergold PJ Gerstenhaber JA Feuerstein G Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
description	Frank C Barone,1 Cezary Marcinkiewicz,2,3 Jie Li,1 Mark Sternberg,3 Peter I Lelkes,2 Dmitriy A Dikin,4 Peter J Bergold,1 Jonathan A Gerstenhaber,2 Giora Feuerstein3 1Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA; 2Department of Bioengineering, Temple University, College of Engineering, Philadelphia, PA, USA; 3Debina Diagnostics Inc, Newtown Square, PA, USA; 4Department of Mechanical Engineering, Temple University, Philadelphia, PA, USA Introduction: We hereby report on studies aimed to characterize safety, pharmacokinetics, and bio-distribution of fluorescent nanodiamond particles (NV)-Z~800 (FNDP-(NV)) administered to rats by intravenous infusion in a single high dose. Methods: Broad scale biological variables were monitored following acute (90 minutes) and subacute (5 or 14 days) exposure to FNDP-(NV). Primary endpoints included morbidity and mortality, while secondary endpoints focused on hematology and clinical biochemistry biomarkers. Particle distribution (liver, spleen, lung, heart, and kidney) was assessed by whole organ near infrared imaging using an in vivo imaging system. This was validated by the quantification of particles extracted from the same organs and visualized by fluorescent and scanning electron microscopy. FNDP-(NV)-treated rats showed no change in morbidity or mortality and preserved normal motor and sensory function, as assessed by six different tests. Results: Blood cell counts and plasma biochemistry remained normal. The particles were principally distributed in the liver and spleen. The liver particle load accounted for 51%, 24%, and 18% at 90 minutes, 5 days, and 14 days, respectively. A pilot study of particle clearance from blood indicated 50% clearance 33 minutes following the end of particle infusion. Conclusion: We concluded that systemic exposure of rats to a single high dose of FDNP-(NV)-Z~800 (60 mg/kg) appeared to be safe and well tolerated over at least 2 weeks. These data suggest that FNDP-(NV) should proceed to preclinical development in the near future. Keywords: fluorescent nanodiamond particles, biocompatibility, near infrared imaging, scanning electron microscopy, neurobehavioral function, pharmacokinetics, rat
format	article
author	Barone FC Marcinkiewicz C Li J Sternberg M Lelkes PI Dikin DA Bergold PJ Gerstenhaber JA Feuerstein G
author_facet	Barone FC Marcinkiewicz C Li J Sternberg M Lelkes PI Dikin DA Bergold PJ Gerstenhaber JA Feuerstein G
author_sort	Barone FC
title	Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
title_short	Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
title_full	Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
title_fullStr	Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
title_full_unstemmed	Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)
title_sort	pilot study on biocompatibility of fluorescent nanodiamond-(nv)-z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part iii)
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/368eac231e1240f3b4032b4f521876f5
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Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III)

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