title: Biodistribution of (125)I-labeled polymeric vaccine carriers after subcutaneous injection.
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.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Riki
authors.initials: R
authors.lastname: Toita
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kanai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watabe
authors.forename: Kenshi
authors.initials: K
authors.lastname: Nakao
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Hatazawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes / Q000737:chemistry; D008027:Light; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012542:Scattering, Radiation; D014018:Tissue Distribution; D014612:Vaccines / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D014612:Vaccines; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid
keywords: (125)I radiolabeled; Biodegradable polymers; Biodistribution; Polymeric nanocarriers; γ-Scintigraphy