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Self-Assembled Polysaccharide Nanogels for Nasal Delivery of Biopharmaceuticals

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Book cover Mucosal Delivery of Biopharmaceuticals

Abstract

Nanogels, nanometer-sized hydrogels with three-dimensional networks, are useful biomaterials for delivery of bioactive molecules (e.g., drug, protein, and nucleic acid) into the targeted tissues. Pullulan, which is a polysaccharide long-chain polymer, forms self-assembled nanogels by introducing cholesterol groups. The cholesteryl group-bearing pullulan (CHP) nanogels are capable of incorporating vaccine antigen in the hydrogels in vitro, and releasing it while keeping its antigenicity and immunogenicity in vivo. One practical advantage of using the CHP nanogels is that the further beneficial properties can be freely added on their original characters. For example, cationic type CHP (cCHP) nanogels, which are bioengineered by adding amine groups to CHP nanogels, enables us to deliver vaccine antigen into the negatively charged nasal epithelium efficiently following nasal administration, resulting in effective uptaking of the antigen by nasal dendritic cells that possesses important roles in inducing the antigen-specific immune responses in nasal mucosa. In this chapter, we review the immunobiological characteristics of cCHP nanogels as potential antigen delivery vehicles for nasal vaccine.

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References

  1. Sasaki Y, Akiyoshi K. Nanogel engineering for new nanobiomaterials: from chaperoning engineering to biomedical applications. Chem Rec. 2010;10(6):366–76.

    CAS  PubMed  Google Scholar 

  2. Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol. 2006;24(10):1211–7.

    Article  CAS  PubMed  Google Scholar 

  3. Akiyoshi K, Kobayashi S, Shichibe S, Mix D, Baudys M, Kim SW, Sunamoto J. Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. J Control Release. 1998;54(3):313–20.

    Article  CAS  PubMed  Google Scholar 

  4. Akiyoshi K, Sasaki Y, Sunamoto J. Molecular chaperone-like activity of hydrogel nanoparticles of hydrophobized pullulan: thermal stabilization with refolding of carbonic anhydrase B. Bioconjug Chem. 1999;10(3):321–4.

    Article  CAS  PubMed  Google Scholar 

  5. Nomura Y, Ikeda M, Yamaguchi N, Aoyama Y, Akiyoshi K. Protein refolding assisted by self-assembled nanogels as novel artificial molecular chaperone. FEBS Lett. 2003;553(3):271–6.

    Article  CAS  PubMed  Google Scholar 

  6. Nomura Y, Sasaki Y, Takagi M, Narita T, Aoyama Y, Akiyoshi K. Thermoresponsive controlled association of protein with a dynamic nanogel of hydrophobized polysaccharide and cyclodextrin: heat shock protein-like activity of artificial molecular chaperone. Biomacromolecules. 2005;6(1):447–52.

    Article  CAS  PubMed  Google Scholar 

  7. Ikeda K, Okada T, Sawada S, Akiyoshi K, Matsuzaki K. Inhibition of the formation of amyloid beta-protein fibrils using biocompatible nanogels as artificial chaperones. FEBS Lett. 2006;580(28–29):6587–95.

    Article  CAS  PubMed  Google Scholar 

  8. Boridy S, Takahashi H, Akiyoshi K, Maysinger D. The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity. Biomaterials. 2009;30(29):5583–91.

    Article  CAS  PubMed  Google Scholar 

  9. Uenaka A, Wada H, Isobe M, Saika T, Tsuji K, Sato E, Sato S, Noguchi Y, Kawabata R, Yasuda T, Doki Y, Kumon H, Iwatsuki K, Shiku H, Monden M, Jungbluth AA, Ritter G, Murphy R, Hoffman E, Old LJ, Nakayama E. T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein. Cancer Immun. 2007;7:9.

    PubMed  Google Scholar 

  10. Kageyama S, Kitano S, Hirayama M, Nagata Y, Imai H, Shiraishi T, Akiyoshi K, Scott AM, Murphy R, Hoffman EW, Old LJ, Katayama N, Shiku H. Humoral immune responses in patients vaccinated with 1–146 HER2 protein complexed with cholesteryl pullulan nanogel. Cancer Sci. 2008;99(3):601–7.

    Article  CAS  PubMed  Google Scholar 

  11. Kunisawa J, Nochi T, Kiyono H. Immunological commonalities and distinctions between airway and digestive immunity. Trends Immunol. 2008;29(11):505–13.

    Article  CAS  PubMed  Google Scholar 

  12. Kiyono H, Fukuyama S. NALT- versus Peyer’s-patch-mediated mucosal immunity. Nat Rev Immunol. 2004;4(9):699–710.

    Article  CAS  PubMed  Google Scholar 

  13. Belshe R, Lee MS, Walker RE, Stoddard J, Mendelman PM. Safety, immunogenicity and efficacy of intranasal, live attenuated influenza vaccine. Expert Rev Vaccines. 2004;3(6):643–54.

    Article  CAS  PubMed  Google Scholar 

  14. Yuki Y, Kiyono H. Mucosal vaccines: novel advances in technology and delivery. Expert Rev Vaccines. 2009;8(8):1083–97.

    Article  CAS  PubMed  Google Scholar 

  15. Carter NJ, Curran MP. Live attenuated influenza vaccine (FluMist(R); Fluenz): a review of its use in the prevention of seasonal influenza in children and adults. Drugs. 2011;71(12):1591–622.

    Article  CAS  PubMed  Google Scholar 

  16. Ambrose CS, Yi T, Falloon J. An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years. Influenza Other Respir Viruses. 2011;5(6):389–97.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Ambrose CS, Walker RE, Connor EM. Live attenuated influenza vaccine in children. Semin Pediatr Infect Dis. 2006;17(4):206–12.

    Article  PubMed  Google Scholar 

  18. Freytag LC, Clements JD. Bacterial toxins as mucosal adjuvants. Curr Top Microbiol Immunol. 1999;236:215–36.

    CAS  PubMed  Google Scholar 

  19. Ryan EJ, McNeela E, Pizza M, Rappuoli R, L. O’Neill, Mills KH. Modulation of innate and acquired immune responses by Escherichia coli heat-labile toxin: distinct pro- and anti-inflammatory effects of the nontoxic AB complex and the enzyme activity. J Immunol. 2000;165(10):5750–9.

    CAS  PubMed  Google Scholar 

  20. Fukuiwa T, Sekine S, Kobayashi R, Suzuki H, Kataoka K, Gilbert RS, Kurono Y, Boyaka PN, Krieg AM, McGhee JR, Fujihashi K. A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity. Vaccine. 2008;26(37):4849–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Yuki Y, Kiyono H. New generation of mucosal adjuvants for the induction of protective immunity. Rev Med Virol. 2003;13(5):293–310.

    Article  CAS  PubMed  Google Scholar 

  22. Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, Spyr C, Steffen R. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. N Engl J Med. 2004;350(9):896–903.

    Article  CAS  PubMed  Google Scholar 

  23. Byrne MP, Smith TJ, Montgomery VA, Smith LA. Purification, potency, and efficacy of the botulinum neurotoxin type A binding domain from Pichia pastoris as a recombinant vaccine candidate. Infect Immun. 1998;66(10):4817–22.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Nochi T, Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. Nat Mater. 2010;9(7):572–8.

    Article  CAS  PubMed  Google Scholar 

  25. Ayame H, Morimoto N, Akiyoshi K. Self-assembled cationic nanogels for intracellular protein delivery. Bioconjug Chem. 2008;19(4):882–90.

    Article  CAS  PubMed  Google Scholar 

  26. Yuki Y, Nochi T, Harada N, Katakai Y, Shibata H, Mejima M, Kohda T, Tokuhara D, Kurokawa S, Takahashi Y, Ono F, Kozaki S, Terao K, Tsukada H, Kiyono H. In vivo molecular imaging analysis of a nasal vaccine that induces protective immunity against botulism in nonhuman primates. J Immunol. 2010;185(9):5436–43.

    Article  CAS  PubMed  Google Scholar 

  27. van Ginkel FW, Jackson RJ, Yuki Y, McGhee JR. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol. 2000;165(9):4778–82.

    CAS  PubMed  Google Scholar 

  28. Nabors GS, Braun PA, Herrmann DJ, Heise ML, Pyle DJ, Gravenstein S, Schilling M, Ferguson LM, Hollingshead SK, Briles DE, Becker RS. Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules. Vaccine. 2000;18(17):1743–54.

    Article  CAS  PubMed  Google Scholar 

  29. Crain MJ, Waltman WD 2nd, Turner JS, Yother J, Talkington DF, McDaniel LS, Gray BM, Briles DE. Pneumococcal surface protein A (PspA) is serologically highly variable and is expressed by all clinically important capsular serotypes of Streptococcus pneumoniae. Infecti Immun. 1990;58(10):3293–9.

    CAS  Google Scholar 

  30. Kong IG, Sato A, Yuki Y, Nochi T, Takahashi H, Sawada S, Mejima M, Kurokawa S, Okada K, Sato S, Briles DE, Kunisawa J, Inoue Y, Yamamoto M, Akiyoshi K, Kiyono H. Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae. Infecti Immun. 2013;81(5):1625–34.

    Article  CAS  Google Scholar 

  31. Lu YJ, Gross J, Bogaert D, Finn A, Bagrade L, Zhang Q, Kolls JK, Srivastava A, Lundgren A, Forte S, Thompson CM, Harney KF, Anderson PW, Lipsitch M, Malley R. Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog. 2008;4(9):e1000159.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Malley R, Trzcinski K, Srivastava A, Thompson CM, Anderson PW, Lipsitch M. CD4 + T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci U S A. 2005;102(13):4848–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8(4):345–50.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Japan Society for the Promotion of Science grants for the Ministry of Education, Culture, Sports, Science, and Technology of Japan for Scientific Research (to H.K.), for the Leading-Edge Research Infrastructure Program (to H.K.), and for the Young Researcher Overseas Visits Program for Vitalizing Brain Circulation (to H.K.).

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Authors and Affiliations

  1. Laboratory of Functional Morphology, Graduate School of Agricultural Science, Tohoku University, Sendai, Miyagi, Japan

    Tomonori Nochi

  2. Division of Mucosal Immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yoshikazu Yuki & Hiroshi Kiyono

  3. International Research and Development Center for Mucosal Vaccines, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Yoshikazu Yuki & Hiroshi Kiyono

  4. Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan

    Yoshikazu Yuki & Hiroshi Kiyono

  5. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan

    Kazunari Akiyoshi

  6. ERATO Bio-nanotransporter Project, Japan Science and Technology Agency, Kyoto, Japan

    Kazunari Akiyoshi

Authors
  1. Tomonori Nochi
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  2. Yoshikazu Yuki
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  3. Kazunari Akiyoshi
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  4. Hiroshi Kiyono
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Corresponding author

Correspondence to Hiroshi Kiyono .

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Editors and Affiliations

  1. IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, CESPU, Gandra, Portugal

    José das Neves

  2. NEWTherapies Group, INEB – Instituto de Engenharia Biomédica, Porto, Portugal

    Bruno Sarmento

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Nochi, T., Yuki, Y., Akiyoshi, K., Kiyono, H. (2014). Self-Assembled Polysaccharide Nanogels for Nasal Delivery of Biopharmaceuticals. In: das Neves, J., Sarmento, B. (eds) Mucosal Delivery of Biopharmaceuticals. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-9524-6_13

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