Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 21, Issue 17, Pages 5310-5315Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2013.06.021
Keywords
Polymeric nanocarriers; Biodegradable polymers; I-125 radiolabeled; gamma-Scintigraphy; Biodistribution
Funding
- CREST from the Japan Science and Technology Agency (JST)
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Polymeric nanoparticles (NPs) comprised of hydrophilic poly(gamma-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (gamma-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered gamma-PGA-Phe NPs. Therefore, we newly synthesized gamma-PGA graft phenylalanine and tyrosine conjugates (gamma-PGA-Phe-Tyr), and then gamma-PGA-Phe-Tyr NPs were labeled with I-125 for monitoring their biodistribution (gamma-PGA-Phe-Tyr(I-125) NPs). Dynamic light scattering (DLS) measurements showed that gamma-PGA-Phe-Tyr(I-125) NPs showed 200 nm in diameter and a negative zeta-potential, which was comparable to those of their precursors. gamma-scintigraphic images showed that in mice, subcutaneously injected gamma-PGA-Phe-Tyr(I-125) NPs were mainly observed at the site of injection (SOI), but not other organs 1 h after administration. However, gamma-PGA-PheTyr(I-125) NPs were almost undetectable at the SOI and other organs at 11 days postinjection. Similar results were observed when gamma-PGA-Phe-Tyr(I-125) NPs were subcutaneously injected into rats. Furthermore, at 11 days postinjection, 73 +/- 3% of the injected dose of gamma-PGA-Phe-Tyr(I-125) NPs was detected in the feces (14 +/- 1%) and urine (59 +/- 1%). These results clearly showed that subcutaneously injected gamma-PGA-Phe-Tyr(I-125) NPs were cleared from the body, and gamma-PGA-Phe NPs were safe and effective vaccine carriers. (C) 2013 Elsevier Ltd. All rights reserved.
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