Physiologically based pharmacokinetic model for predicting the biodistribution of albumin nanoparticles after induction and recovery from acute lung injury
Elena O. Kutumova,
Ilya R. Akberdin,
Vera S. Egorova,
Ekaterina P. Kolesova,
Alessandro Parodi,
Vadim S. Pokrovsky,
Andrey A. Zamyatnin, Jr,
Fedor A. Kolpakov
Affiliations
Elena O. Kutumova
Department of Computational Biology, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia; Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090, Novosibirsk, Russia; Biosoft.Ru, Ltd., 630058, Novosibirsk, Russia
Ilya R. Akberdin
Department of Computational Biology, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia; Biosoft.Ru, Ltd., 630058, Novosibirsk, Russia; Department of Natural Sciences, Novosibirsk State University, 630090, Novosibirsk, Russia
Vera S. Egorova
Scientific Center for Translational Medicine, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia
Ekaterina P. Kolesova
Scientific Center for Translational Medicine, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia
Alessandro Parodi
Scientific Center for Translational Medicine, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia; Corresponding author. Scientific Center for Translational Medicine, Sirius University of Science and Technology, Olympic Ave, 1, Bolshoy Sochi, Krasnodar Krai, 354340, Sirius, Krasnodar Region, Russia
Vadim S. Pokrovsky
N.N. Blokhin Medical Research Center of Oncology, 115522, Moscow, Russia; Patrice Lumumba People's Friendship University, 117198, Moscow, Russia
Andrey A. Zamyatnin, Jr
Scientific Center for Translational Medicine, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia; Faculty of Bioengineering and Bioinformatics and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234, Moscow, Russia; Department of Biological Chemistry, Sechenov First Moscow State Medical University, 119991, Moscow, Russia; Corresponding author. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie gory 1-73, 119234, Moscow, Russia
Fedor A. Kolpakov
Department of Computational Biology, Sirius University of Science and Technology, 354340, Sirius, Krasnodar Region, Russia; Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090, Novosibirsk, Russia; Biosoft.Ru, Ltd., 630058, Novosibirsk, Russia
The application of nanomedicine in the treatment of acute lung injury (ALI) has great potential for the development of new therapeutic strategies. To gain insight into the kinetics of nanocarrier distribution upon time-dependent changes in tissue permeability after ALI induction in mice, we developed a physiologically based pharmacokinetic model for albumin nanoparticles (ANP). The model was calibrated using data from mice treated with intraperitoneal LPS (6 mg/kg), followed by intravenous ANP (0.5 mg/mouse or about 20.8 mg/kg) at 0.5, 6, and 24 h. The simulation results reproduced the experimental observations and indicated that the accumulation of ANP in the lungs increased, reaching a peak 6 h after LPS injury, whereas it decreased in the liver, kidney, and spleen. The model predicted that LPS caused an immediate (within the first 30 min) dramatic increase in lung and kidney tissue permeability, whereas splenic tissue permeability gradually increased over 24 h after LPS injection. This information can be used to design new therapies targeting specific organs affected by bacterial infections and potentially by other inflammatory insults.
