TY - JOUR

T1 - Physiologically based pharmacokinetic model for predicting the biodistribution of albumin nanoparticles after induction and recovery from acute lung injury

AU - Кутумова, Елена Олеговна

AU - Акбердин, Илья Ринатович

AU - Egorova, Vera S.

AU - Kolesova, Ekaterina P.

AU - Parodi, Alessandro

AU - Pokrovsky, Vadim S.

AU - Zamyatnin Jr., Andrey A.

AU - Колпаков, Федор А.

N1 - This research was funded by the Russian Science Foundation (grant no. 21-75-30020). V.S.P. was supported by State Program of the Ministry of Science and Higher Education of the Russian Federation (no. 075-01551-23-00; FSSF-2023-0006). © 2024 Published by Elsevier Ltd.

PY - 2024/5/30

Y1 - 2024/5/30

N2 - 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.

AB - 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.

KW - Acute lung injury

KW - Albumin nanoparticle biodistribution

KW - BioUML

KW - Lipopolysaccharide injection

KW - Murine model

KW - Nanomedicine

KW - PBPK modeling

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85193076638&origin=inward&txGid=c32204390e9464d38d18231d2e192216

UR - https://www.mendeley.com/catalogue/6bff9b22-f590-35f0-8323-8c7f10d5a8bb/

U2 - 10.1016/j.heliyon.2024.e30962

DO - 10.1016/j.heliyon.2024.e30962

M3 - Article

C2 - 38803942

VL - 10

JO - Heliyon

JF - Heliyon

SN - 2405-8440

IS - 10

M1 - e30962

ER -