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

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.

Nanodiamond-enhanced MRI via in situ hyperpolarization

“…Studying the retention of NDs in the liver at present requires organ harvesting, which limits long-term studies4552. We estimate that for NDs to be present at 1 mg ml −1 in a 3 ml mouse liver53 would require injection of 5 mg of ND into a 20 g mouse, assuming 60% accumulation in the liver5354.…”

Nanodiamond–Gadolinium(III) Aggregates for Tracking Cancer Growth In Vivo at High Field

“…28,29 In contrast to other carbon-based nanomaterials, detonation nanodiamonds (NDs) have great potential for a variety of in vivo applications. 30–35 NDs are 4–6 nm carbon particles with a diamond crystal structure. 30,36,37 NDs are biocompatible; can carry a broad range of therapeutics; are dispersible in water; and allow uniform, scalable production.…”

“…30,35,38 Nanodiamonds were recently analyzed for biocompatibility in rats and nonhuman primates and shown to be nontoxic over 6 months by comprehensive analysis of serum, urine, histology, and body weight. 35 …”

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen–nanodiamond hydrogel

“…For its potential clinical use in the future, we have rigorously studied its properties to ensure its safety and feasibility. NDs were safely cleared through urinary and digestive excretion, depending on the mode of administration (23,35,64,65). Importantly, ND vehicles complexed with gadolinium-based magnetic resonance imaging agents have resulted in being among the highest ever reported per-gadolinium relaxivity values (21).…”

“…Importantly, ND vehicles complexed with gadolinium-based magnetic resonance imaging agents have resulted in being among the highest ever reported per-gadolinium relaxivity values (21). In addition, ND safety and biocompatibility have been recently demonstrated in a nonhuman primate study involving systemic administration of NDs to both genders, where no apparent toxicity or impaired organ function was observed (64). Similarly, the safety and biocompatibility of hydrogels allow for their versatile applications in tissue engineering (36)(37)(38)66).…”