Mathematical modelling of nanoparticle biodistribution: extrapolation among intravenous, oral and pulmonary administration routes

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.

[1]  J. Grothaus,et al.  Tissue distribution of 20 nm, 100 nm and 1000 nm fluorescent polystyrene latex nanospheres following acute systemic or acute and repeat airway exposure in the rat. , 2009, Toxicology.

[2]  Gregory T. Reeves,et al.  Biological Systems from an Engineer's Point of View , 2009, PLoS biology.

[3]  D. Hamby.  A review of techniques for parameter sensitivity analysis of environmental models , 1994, Environmental monitoring and assessment.

[4]  M F Hoylaerts,et al.  Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. , 2001, American journal of respiratory and critical care medicine.

[5]  Robert Gelein,et al.  EXTRAPULMONARY TRANSLOCATION OF ULTRAFINE CARBON PARTICLES FOLLOWING WHOLE-BODY INHALATION EXPOSURE OF RATS , 2002, Journal of toxicology and environmental health. Part A.

[6]  L. Yengo,et al.  Combined global sensitivity analysis and population PBPK modeling for assessing consistency of TCDD toxicokinetics data in mice , 2010 .

[7]  R. Sturm,et al.  Stochastic Modeling Predictions for the Clearance of Insoluble Particles from the Tracheobronchial Tree of the Human Lung , 2007, Bulletin of mathematical biology.

[8]  P. Couvreur,et al.  Lymphatic Targeting of Polymeric Nanoparticles After Intraperitoneal Administration in Rats , 1992, Pharmaceutical Research.

[9]  M. Prato,et al.  Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Yves-Jacques Schneider,et al.  Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Kostas Kostarelos,et al.  Physiologically based pharmacokinetic modeling of nanoparticles. , 2010, ACS nano.

[12]  Agnes G Oomen,et al.  What do we (need to) know about the kinetic properties of nanoparticles in the body? , 2007, Regulatory toxicology and pharmacology : RTP.

[13]  J. Cheon,et al.  Pharmacokinetic properties and tissue storage of FITC conjugated SA-MnMEIO nanoparticles in mice , 2009 .

[14]  Byron Ballou,et al.  Noninvasive imaging of quantum dots in mice. , 2004, Bioconjugate chemistry.

[15]  Mina Choi,et al.  The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. , 2009, Toxicology letters.

[16]  A. Florence.  Issues in Oral Nanoparticle Drug Carrier Uptake and Targeting , 2004, Journal of drug targeting.

[17]  A. Rolland,et al.  Blood clearance and organ distribution of intravenously administered polymethacrylic nanoparticles in mice. , 1989, Journal of pharmaceutical sciences.

[18]  Petra Krystek,et al.  Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. , 2008, Biomaterials.

[19]  Ivan Nestorov,et al.  Whole Body Pharmacokinetic Models , 2003, Clinical pharmacokinetics.

[20]  K. Kisich,et al.  The potential advantages of nanoparticle drug delivery systems in chemotherapy of tuberculosis. , 2005, American journal of respiratory and critical care medicine.

[21]  H. Swai,et al.  In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[22]  Scott E McNeil,et al.  Nanotechnology safety concerns revisited. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  O. Preining.  The physical nature of very, very small particles and its impact on their behaviour , 1998 .

[24]  Robert Sturm,et al.  A computer model for the clearance of insoluble particles from the tracheobronchial tree of the human lung , 2007, Comput. Biol. Medicine.

[25]  Si-Shen Feng,et al.  Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. , 2005, Biomaterials.

[26]  Nakissa Sadrieh,et al.  Regulatory perspective on the importance of ADME assessment of nanoscale material containing drugs. , 2009, Advanced drug delivery reviews.

[27]  E. Kuempel,et al.  Development of a bio-mathematical model in rats to describe clearance, retention and translocation of inhaled nano particles throughout the body , 2009 .

[28]  H. Ando,et al.  Circulation time and body distribution of 14C-labeled amino-modified polystyrene nanoparticles in mice. , 1995, Journal of pharmaceutical sciences.

[29]  Ian Cousins,et al.  Development and application of a generalized physiologically based pharmacokinetic model for multiple environmental contaminants , 2003, Environmental toxicology and chemistry.

[30]  Ming-Hsien Tsai,et al.  Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice. , 2008, Environmental science & technology.

[31]  R M Albrecht,et al.  Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. , 2001, Journal of pharmaceutical sciences.