TY - JOUR
T1 - Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats
T2 - Safety, pharmacokinetics, and bio-distribution (Part III)
AU - Barone, Frank C.
AU - Marcinkiewicz, Cezary
AU - Li, Jie
AU - Sternberg, Mark
AU - Lelkes, Peter I.
AU - Dikin, Dmitriy A.
AU - Bergold, Peter J.
AU - Gerstenhaber, Jonathan A.
AU - Feuerstein, Giora
N1 - Publisher Copyright:
© 2018 Barone et al.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Biocompatibility
KW - Fluorescent nanodiamond particles
KW - Near infrared imaging
KW - Neurobehavioral function
KW - Pharmacokinetics
KW - Rat
KW - Scanning electron microscopy
UR - http://www.scopus.com/inward/record.url?scp=85054351174&partnerID=8YFLogxK
U2 - 10.2147/IJN.S171117
DO - 10.2147/IJN.S171117
M3 - Article
SN - 1176-9114
VL - 13
SP - 5449
EP - 5468
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -