Abstract:
PURPOSE:To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model. METHODS:400 ug of CNDs is injected intravenously to mice bearing melanoma cell lines. Gold content is determined from plasma and tissue samples using neutron activation analysis. A physiologically based pharmacokinetic (PBPK) model is developed for 5 nm positive, negative, and neutral and 11 nm negative nanoparticles and extrapolated to 22 nm positive particles. A global sensitivity analysis is performed for estimated model parameters. RESULTS:Negative and neutral particles exhibited similar distribution profiles. Unique model parameter estimates and distribution profiles explain similarities and differences relative to positive particles. The model also explains mechanisms of elimination by kidney and reticuloendothelial uptake in liver and spleen, which varies with particle size and charge. CONCLUSION:Since the PBPK model can capture the diverse temporal profiles of non-targeted nanoparticles, we propose that when specific binding ligands are lacking, size and charge of nanodevices govern most of their in vivo interactions.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Mager DE,Mody V,Xu C,Forrest A,Lesniak WG,Nigavekar SS,Kariapper MT,Minc L,Khan MK,Balogh LPdoi
10.1007/s11095-012-0784-7subject
Has Abstractpub_date
2012-09-01 00:00:00pages
2534-42issue
9eissn
0724-8741issn
1573-904Xjournal_volume
29pub_type
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