*3.6. Maximum Tolerated Dose of N-AI-Loaded Liposomes in Mice*

*N*-AI liposomes were well-tolerated in mice, when given as an intravenous (i.v.) single bolus dose up to 20 mg/kg *N*-AI or multiple fractionated dose, up to 100 mg/kg *N*-AI. This exceeded that of free *N*-AI, which had a maximum tolerated single bolus dose of 8.5 mg/kg (Supplementary Information Figure S4). Mice treated with free drug at concentrations above 8.5 mg/kg, as well as the equivalent volume of the DMSO/PBS vehicle without drug, displayed adverse signs of intolerance immediately upon injection, including lethargy, hind-leg paralysis, tremors, and difficulty breathing [36,37], preventing higher concentrations of free *N*-AI from being tested. Liposome encapsulation therefore provided an injectable formulation of *N*-AI, with improved tolerability than the free drug.
