Polymeric nanoparticles (NPs) comprised of hydrophilic poly(γ- glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (γ-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered γ-PGA-Phe NPs. Therefore, we newly synthesized γ-PGA graft phenylalanine and tyrosine conjugates (γ-PGA-Phe-Tyr), and then γ-PGA-Phe-Tyr NPs were labeled with 125I for monitoring their biodistribution (γ-PGA-Phe-Tyr(125I) NPs). Dynamic light scattering (DLS) measurements showed that γ-PGA-Phe-Tyr(125I) NPs showed 200 nm in diameter and a negative ζ-potential, which was comparable to those of their precursors. γ-scintigraphic images showed that in mice, subcutaneously injected γ-PGA-Phe-Tyr(125I) NPs were mainly observed at the site of injection (SOI), but not other organs 1 h after administration. However, γ-PGA-PheTyr(125I) NPs were almost undetectable at the SOI and other organs at 11 days postinjection. Similar results were observed when γ-PGA-Phe-Tyr(125I) NPs were subcutaneously injected into rats. Furthermore, at 11 days postinjection, 73 ± 3% of the injected dose of γ-PGA-Phe-Tyr(125I) NPs was detected in the feces (14 ± 1%) and urine (59 ± 1%). These results clearly showed that subcutaneously injected γ-PGA-Phe-Tyr( 125I) NPs were cleared from the body, and γ-PGA-Phe NPs were safe and effective vaccine carriers.
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