Abstract:
: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 (125)I for monitoring their biodistribution (γ-PGA-Phe-Tyr((125)I) NPs). Dynamic light scattering (DLS) measurements showed that γ-PGA-Phe-Tyr((125)I) NPs showed 200nm 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((125)I) NPs were mainly observed at the site of injection (SOI), but not other organs 1h after administration. However, γ-PGA-PheTyr((125)I) NPs were almost undetectable at the SOI and other organs at 11days postinjection. Similar results were observed when γ-PGA-Phe-Tyr((125)I) NPs were subcutaneously injected into rats. Furthermore, at 11days postinjection, 73±3% of the injected dose of γ-PGA-Phe-Tyr((125)I) NPs was detected in the feces (14±1%) and urine (59±1%). These results clearly showed that subcutaneously injected γ-PGA-Phe-Tyr((125)I) NPs were cleared from the body, and γ-PGA-Phe NPs were safe and effective vaccine carriers.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Toita R,Kanai Y,Watabe H,Nakao K,Yamamoto S,Hatazawa J,Akashi Mdoi
10.1016/j.bmc.2013.06.021subject
Has Abstractpub_date
2013-09-01 00:00:00pages
5310-5issue
17eissn
0968-0896issn
1464-3391pii
S0968-0896(13)00552-Xjournal_volume
21pub_type
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