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Kuo, Timothy Ting-Chang

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Kuo

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Timothy Ting-Chang

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Kuo, Timothy Ting-Chang

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2010 - 20132

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    Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery
    (American Association for the Advancement of Science (AAAS), 2013) Pridgen, E. M.; Alexis, F.; Kuo, Timothy Ting-Chang; Levy-Nissenbaum, E.; Karnik, R.; Blumberg, Richard; Langer, Robert; Farokhzad, Omid
    Nanoparticles are poised to have a tremendous impact on the treatment of many diseases, but their broad application is limited because currently they can only be administered by parenteral methods. Oral administration of nanoparticles is preferred but remains a challenge because transport across the intestinal epithelium is limited. Here, we show that nanoparticles targeted to the neonatal Fc receptor (FcRn), which is known to mediate the transport of IgG antibodies across epithelial barriers, are efficiently transported across the intestinal epithelium using both in vitro and in vivo models. In mice, orally administered FcRn-targeted nanoparticles crossed the intestinal epithelium and reached systemic circulation with a mean absorption efficiency of 13.7%*h compared with only 1.2%*h for non-targeted nanoparticles. In addition, targeted nanoparticles containing insulin as a model nanoparticle-based therapy for diabetes were orally administered at a clinically relevant insulin dose of 1.1 U/kg and elicited a prolonged hypoglycemic response in wild-type mice. This effect was abolished in FcRn knockout mice, indicating the enhanced nanoparticle transport was due specifically to FcRn. FcRn-targeted nanoparticles may have a major impact on the treatment of many diseases by enabling drugs currently limited by low bioavailability to be efficiently delivered though oral administration.
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    Neonatal Fc Receptor: From Immunity to Therapeutics
    (Springer US, 2010) Kuo, Timothy Ting-Chang; Baker, Kristi; Yoshida, Masaru; Qiao, Shuo-Wang; Aveson, Victoria G.; Lencer, Wayne; Blumberg, Richard
    The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn.