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ACS Nano. 2016 Aug 23;10(8):7385-400. doi: 10.1021/acsnano.6b00839. Epub 2016 Jul 22.

Biocompatibility Assessment of Detonation Nanodiamond in Non-Human Primates and Rats Using Histological, Hematologic, and Urine Analysis.

Author information

1
Department of Biomedical Engineering, Northwestern University , Evanston, Illinois 60208, United States.
2
Department of Biomedical Engineering, Peking University , Beijing, China 100871.
3
Alverno Clinical Laboratories , Hammond, Indiana 46324, United States.
4
NanoCarbon Research Institute, Asama Research Extension Centre, Shinshu University , Ueda, Nagano 386-8567, Japan.
5
Life Sciences Group, IIT Research Institute , Chicago, Illinois 60616, United States.
6
Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117599.
7
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore 117600.

Abstract

Detonation nanodiamonds (DNDs) have been widely explored for biomedical applications ranging from cancer therapy to magnetic resonance imaging due to several promising properties. These include faceted surfaces that mediate potent drug binding and water coordination that have resulted in marked enhancements to the efficacy and safety of drug delivery and imaging. In addition, scalable processing of DNDs yields uniform particles. Furthermore, a broad spectrum of biocompatibility studies has shown that DNDs appear to be well-tolerated. Prior to the clinical translation of DNDs for indications that are addressed via intravenous administration, comprehensive assessment of DND safety in both small and large animal preclinical models is needed. This article reports the results of a DND biocompatibility study in both non-human primates and rats. The rat study was performed as a multiple dose subacute investigation in two cohorts that lasted for 2 weeks and included histological, serum, and urine analysis. The non-human primate study was performed as a dual gender, multiple dose, and long-term investigation in both standard/clinically relevant and elevated dosing cohorts that lasted for 6 months and included comprehensive serum, urine, histological, and body weight analysis. The results from these studies indicate that NDs are well-tolerated at clinically relevant doses. Examination of dose-dependent changes in biomarker levels provides important guidance for the downstream in-human validation of DNDs for clinical drug delivery and imaging.

KEYWORDS:

biocompatibility; biomaterial; carbon; nanodiamond; nanomedicine

PMID:
27439019
DOI:
10.1021/acsnano.6b00839
[Indexed for MEDLINE]

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