Table 1.

Selected PBPK model structures for nanoparticles.

Reference	Nanopartic	Dosing route	Species	Modeling entity	Tissues considered	Clearance mechanism	Tissue models
Kagan, Gershkovich et al. 2014106	AmBisome®	IV	Mice, rats	Liposomal amphotericin B (AmB) and free AmB	Plasma, liver, spleen, kidneys, GI tract, lungs, heart, and the remainders	Clearance of free AmB was defined in the liver, the kidneys, and the remainder compartment	In the spleen and kidneys: In others:
Li, Johanson et al. 201421	PEG-coated polyacrylamide nanoparticle	IV	Rats	Nanoparticle	Arterial blood, venous blood, lungs, bone marrow, brain, heart, kidneys, liver, spleen, and the remainders	Biodegradation was considered to be negligible. Clearance was defined in the kidneys and the liver.	In blood: In organs:
Lin, Monteiro- Riviere et al. 2016111	PEG-coated gold nanoparticles	IV	Mice	Nanoparticle	Arterial plasma, venous plasma, lungs, brain, spleen, liver, kidneys, and the remainders	Metabolism and dissolution were not considered. Clearance was defined in the kidneys and the liver.	In the brain and the rest of the body: In the lung, spleen, liver, and kidneys for 13 nm nanoparticles: For 100 nm nanoparticle:
Lin, Monteiro-Riviere et al. 2016112	PEG-coated gold nanoparticles	IV	Mice, rats, and pigs	Nanoparticle	Arterial plasma, venous plasma, lungs, spleen, liver, kidneys, brain, and the remainders	Metabolism and dissolution were not considered. Clearance was defined in the kidneys and the liver.	In the brain: In others:
Sweeney, MacCalman et al. 201527	Iridium nanoparticles, sliver nanoparticles, titanium dioxide nanoparticles	Inhalation	Rats	Nanoparticle	Arterial blood, venous blood, olfactory region, upper airways, alveolar region, interstitium, lymph nodes, GI tract, liver, spleen, kidneys, heart, brain, and the remainders	Clearance was defined in the kidneys and the liver.	In the liver: In others: