Table 2.

Commonly used surfactants in parenteral nanosuspensions with their daily uptake limits.

Nos.	Ingredient	Chemical structure (Monomeric units)n	GRAS status and daily uptake limits with a particular route of administration	IIG limit (maximum potency/unit dose)	Refs.
1	Hydroxypropyl cellulose (HPC)		•Not specified by WHO for human use •Lethal dose, 50% (LD50) (rat intravenous administration: 0.25 g/kg)	*	52, 68
2	Hypromellose (HPMC)		•Estimated daily intake (EDI) of 5.50 g for Human •LD50 (mouse, IP): 5 g/kg •LD50 (rat, IP): 5.2 g/kg	*	52, 68
3	Leucine		•It is generally regarded as a nontoxic and non-irritant material •Only moderately toxic by the subcutaneous route. •LD50 (rat, IP): 5.379 g/kg	IV-52.6%	52, 69, 70
4	Poloxamer F68, F127		•No adverse effects at IV administration up to 0.5 g/kg/day in dogs •0.5 g/kg/day to rabbits •LD50 (mouse, IP): 1 g/kg, •LD50 (rat, IV): 7.5 g/kg	Poloxamer F68:	52, 68
				IM-0.2%,
				IV-0.6%,
5	Polyethyleneglycol (PEG) 400		•The WHO has set an estimated acceptable daily intake of polyethylene glycols at up to 10 mg/kg body-weight •LD50 (mouse, IV): 8.6 g/kg •LD50 (rat, IV): 7.3 g/kg	IM-20%,	52, 68
				IV-75.58%
6	Polysorbate 80		•The WHO has set an estimated acceptable daily intake for polysorbates 25 mg/kg body-weight •LD50 (mouse, IV): 4.5 g/kg •LD50 (rat, IV): 1.8 g/kg	IM-12%,	52, 68
				IV infusion-58.5%
7	Polyvinylalcohol (PVA)		•PVA is generally considered a nontoxic material •LD50 (mouse, oral): 14.7 g/kg •LD50 (rat, oral): > 20 g/kg	Intravitreal-0.12 mg	52, 68
8	Povidon		•A temporary acceptable daily intake for povidone has been set by the WHO at up to 25 mg/kg body-weight. •LD50 (mouse, IP): 12 g/kg	IV-0.2%, IM-0.9%	52, 68
9	2-Pyrrolidone		•Poisonous by IV route. Toxic by ingestion, skin contact, and IP routes. It is an experimental teratogenic, mutagenic additive •LD50 (mouse, IV): 0.155 g/kg •LD50 (mouse, oral): 5.13 g/kg •LD50 (rabbit, SC): 8.0 g/kg •LD50 (rat, IP): 2.472 g/kg •LD50 (rat, IV): 0.0805 g/kg	SC-25.85%	52, 68
10	Sodium lauryl sulfate (SLS)		•Should not be used by IV route •LD50 0.5–5.0 g/kg	*	52, 68
11	Cross povidone		•Acceptable daily intake in humans has not been specified by the WHO. •LD50 (mouse, IP): 12 g/kg	IM-0.02%	52, 68
12	Chitosan		•Chitosan has been shown to be biodegradable. •LD50 (mouse, oral): >16 g/kg	*	52
13	Cyclodextrin		•Cyclodextrin-α: LD50 (rat, IP): 1.0 g/kg •LD50 (rat, IV): 0.79 g/kg •Cyclodextrin-β: LD50 (mouse, IP): 0.33 g/kg •LD50 (mouse, SC): 0.41 g/kg •LD50 (rat, IP): 0.36 g/kg •LD50 (rat, IV): 1.0 g/kg •LD50 (rat, oral): 18.8 g/kg •LD50 (rat, SC): 3.7 g/kg •Cyclodextrin-γ: LD50 (rat, IP): 4.6 g/kg •LD50 (rat, IV): 4.0 g/kg •LD50 (rat, oral): 8.0 g/kg	IV-5%	52, 68
14	d-α-Tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS)		•The WHO has set an acceptable daily intake of tocopherol used as an antioxidant at 0.15–2.0 mg/kg body-weight	IV-225 mg/L	52, 68
15	Arginine		•Oral supplementation with l-arginine at doses up to 20 g daily are generally well tolerated	IM-78%,	52, 68, 71, 72
				IV-39.5%
16	Proline		•Generally regarded as safe	IV infusion-35.6%	73, 51, 68
17	Serum albumin		•Essentially nontoxic and non-irritant •LD50 (monkey, IV): >12.5 g/kg •LD50 (rat, IV): >12.5 g/kg	IV-2%	52, 68
18	Soluplus®		*	*	74, 75

^*Parameter not found in the literature. SC, Subcutaneous; IM, Intramuscular; IV, Intravenous; IP, Intraperitoneal