. 2019 Oct 1;10(1):1–12. doi: 10.1016/j.jpha.2019.09.003

Table 1.

In vivo studies conducted with nanodiamonds.

S.No.	Parameter for biocompatibility	Observations based on parameters	Model organism	Nanodiamond type with size	In vivo study results
1.	Survival	1. Cytotoxicity and in vivo toxicity	1. Human embryonic kidney 293 (HEK293) cells 2. Xenopus laevis embryos	FND (4 nm)	Chemically surface functionalized (-OH, -NH2 or -CO2H) ND related cytotoxicity and in vivo toxicity of ND were prepared. They used two model systems viz. human embryonic kidney 293 (HEK293) cells and Xenopus laevis embryos. The results of cell viability assays revealed that ND were not 1. cytotoxic to HEK293 cells at below 50 μg/mL ND 2. Having a potential embryotoxicity and teratogenicity for carboxylated ND-CO₂H [40].
1.	Survival	2. Mortality rate	Bivalvae	DND (4–6 nm)	100% mortality when exposed to ND solutions of 10 g/L [33].
2.	Morphology	1. Embryonic development 2. Histological examination	Zebrafish embryo	DND (100 nm)	A concentration dependent higher malformation induction after ND-COOH micro injection [34].
			Cynomolgus monkey (Macaca fascicularis)	DND	Some substantial abnormalities in monkey heart and liver at higher doses. Mild abnormalities at normal doses.
			Rat (Rattus norvegicus)		No abnormal liver or kidney function histological changes.
			Xenograft SCID mice	ND-paclitaxel	Preservation of anticancer activities on the induction of mitotic blockage and apoptosis [35].
3.	Biodistribution	Accumulation	Rat	NDs	1. Radio labeled diamond nanoparticles gets accumulated majorly in lung, spleen and liver and finally gets excreted into the urinary tract. 2. An inflammatory response in the lungs and high dose- dependent retention of NDs in the lung [25].
					NDs retention and accumulation in the macrophages present in the liver [9].
			Mice	FND	Accumulation in the axillary lymph nodes [36].
4.	Metabolism	1. Biochemical parameter 2. Oxidative stress markers	Rats and monkeys	ND	1. Some histological alterations but no organ dysfunction. 2. Some changes in blood biochemical parameters affecting the liver function and lipid metabolism, but no signs of cell destruction [37].
4.	Metabolism	1. Biochemical parameter 2. Oxidative stress markers	Murine	ND	Increased activity of glutathione S- transferase on 7 day and catalase on 14 day were observed respectively [38].