Biodistribution of ¹²⁵I-labeled polymeric vaccine carriers after subcutaneous injection

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• 作者：Riki Toita ; Yasukazu Kanai ; Hiroshi Watabe ; Kenshi Nakao ; Seiichi Yamamoto ; Jun Hatazawa ; Mitsuru Akashi
• 关键词：Polymeric nanocarriers ; Biodegradable polymers ; 125I radiolabeled ; ¦Ã-Scintigraphy ; Biodistribution
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：21
• 期：17
• 页码：5310-5315
• 全文大小：1001 K

文摘

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