3H dendrimer nanoparticle organ/tumor distribution

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. Neutral (NSD) and positive surface charged (PSD) generation 5 (d = 5 nm) PAMAM dendrimers were synthesized by using 3H-label...

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Bibliographic Details
Published inPharmaceutical research Vol. 21; no. 3; p. 476
Main Authors Nigavekar, Shraddha S, Sung, Lok Yun, Llanes, Mikel, El-Jawahri, Areej, Lawrence, Theodore S, Becker, Christopher W, Balogh, Lajos, Khan, Mohamed K
Format Journal Article
LanguageEnglish
Published United States 01.03.2004
Subjects
Animals
Dendrimers
Humans
Melanoma
Melanoma, Experimental
Nanoparticles
Tissue Distribution
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Summary: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. 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. 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. 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.
ISSN:0724-8741