Physiologically based pharmacokinetic model for composite nanodevices: effect of charge and size on in vivo disposition.
OBJECTIVE
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.


CONCLUSIONS
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.
Dept. of Pharmaceutical Sciences,, University at Buffalo SUNY, Buffalo, New York 14260, USA.
Donald E
DE
Mager
Vidhi
V
Mody
Chao
C
Xu
Alan
A
Forrest
Wojciech G
WG
Lesniak
Shraddha S
SS
Nigavekar
Muhammed T
MT
Kariapper
Leah
L
Minc
Mohamed K
MK
Khan
Lajos P
LP
Balogh
D000818:Animals; D045744:Cell Line, Tumor; D051379:Mice; D008962:Models, Theoretical; D036103:Nanotechnology; D010316:Particle Size; D010599:Pharmacokinetics