3H dendrimer nanoparticle organ/tumor distribution.
OBJECTIVE
To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.


METHODS
Neutral (NSD) and positive surface charged (PSD) generation 5 (d = 5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples. Mice were also monitored for acute toxicity.


RESULTS
Both PSD and NSD localized to major organs and tumor. Dendrimers cleared rapidly from blood, with deposition peaking at 1 h for most organs and stabilizing from 24 h to 7 days postinjection. Maximal excretion occurred via urine within 24 h postinjection. Neither dendrimer showed acute toxicity.


CONCLUSIONS
Changes in the net surface charge of polycationic PAMAMs modify their biodistribution. PSD deposition into tissues is higher than NSD, although the biodistribution trend is similar. Highest levels were found in lungs, liver, and kidney, followed by those in tumor, heart, pancreas, and spleen, while lowest levels were found in brain. These nanoparticles could have future utility as systemic biomedical delivery devices.
Nigavekar
Shraddha S
SS
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Sung
Lok Yun
LY
Llanes
Mikel
M
El-Jawahri
Areej
A
Lawrence
Theodore S
TS
Becker
Christopher W
CW
Balogh
Lajos
L
Khan
Mohamed K
MK
D000818:Animals; D050091:Dendrimers; D006801:Humans; D008545:Melanoma; D008546:Melanoma, Experimental; D053758:Nanoparticles; D014018:Tissue Distribution
D050091:Dendrimers