Title: Mathematical modelling of nanoparticle biodistribution: extrapolation among intravenous, oral and pulmonary administration routes
Author: Mingguang Li, Joshua Reineke
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA
Abstract: In this study, a physiological-based mathematical model was developed to describe and compare the absorption, distribution, metabolism, and elimination (ADME) of nanoparticles after intravenous (IV), oral, and pulmonary exposure. The development of the model was based on physiological principles, compartmental analysis, and mathematical modelling. The human body was separated into compartments and their mass-time profiles were simulated. Mathematical equations describing the intercompartmental transportation of nanoparticles were developed based on first order kinetics. Nanoparticle biodistribution in all the tissues and organs was analysed for comparison among the administration routes. Sensitivity of transportation coefficients were calculated for evaluation of their relative importance to the output of the model. The model indicates some interesting aspects of administration route extrapolation, explains many published observations of nanoparticle ADME and proves to give a comprehensive understanding of nanoparticle ADME compared to traditional pharmacokinetic models.
Keywords: physiologically-based pharmacokinetic models; nanoparticles; nanoparticle biodistribution; oral exposure; intravenous exposure; IV exposure; pulmonary exposure; sensitivity analysis; mathematical modelling; human tissue; human organs; administration routes; nanoparticle absorption; nanoparticle distribution; nanoparticle metabolism; nanoparticle elimination.
Int. J. of Nano and Biomaterials, 2011 Vol.3, No.3, pp.222 - 238
Available online: 28 Aug 2011