Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates

Yoshikazu Yuki; Norihiro Harada; Shin-Ichi Sawada; Yohei Uchida; Rika Nakahashi-Ouchida; Hiromi Mori; Tomoyuki Yamanoue; Tomonori Machita; Masakatsu Kanazawa; Dai Fukumoto; Hiroyuki Ohba; Takashi Miyazaki; Kazunari Akiyoshi; Kohtaro Fujihashi; Hiroshi Kiyono

doi:10.1016/j.vaccine.2023.06.065

Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates

Vaccine. 2023 Jul 31;41(34):4941-4949. doi: 10.1016/j.vaccine.2023.06.065. Epub 2023 Jun 27.

Authors

Affiliations

¹ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; HanaVax Inc, Tokyo, Japan; Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba, Japan. Electronic address: yukiy@ims.u-tokyo.ac.jp.
² Central Research Laboratory, Hamamatsu Photonics K.K, Shizuoka, Japan.
³ Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan; Future Mucosal Vaccine Research and Development Synergy Institute, Chiba University, Chiba, Japan.
⁴ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba, Japan.
⁵ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba, Japan; Future Mucosal Vaccine Research and Development Synergy Institute, Chiba University, Chiba, Japan.
⁶ Toko Yakuhin Kogyo Co., Ltd, Japan.
⁷ Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
⁸ Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba, Japan; Future Mucosal Vaccine Research and Development Synergy Institute, Chiba University, Chiba, Japan; Division of Mucosal Vaccines, International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, USA.
⁹ Division of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; HanaVax Inc, Tokyo, Japan; Future Mucosal Vaccine Research and Development Synergy Institute, Chiba University, Chiba, Japan; Mucosal Immunology and Allergy Therapeutics, Institute for Global Prominent Research, Future Medicine Education and Research Organization, Chiba University, Chiba, Japan; CU-UCSD Center for Mucosal Immunology, Allergy, and Vaccine (cMAV) Division of Gastroenterology, Department of Medicine, University of California, San Diego, CA, USA.

PMID: 37385890
DOI: 10.1016/j.vaccine.2023.06.065

Abstract

Cationic cholesteryl-group-bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with ¹⁸F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to ¹⁸F or ¹¹¹In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.

Keywords: Biodistribution; Drug delivery system; Mouse; Nasal vaccine; Non-human primate; Positron emission tomography (PET).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intranasal
Animals
Drug Delivery Systems*
Macaca mulatta
Nanogels
Pneumococcal Vaccines*
Tissue Distribution

Substances

polyethylene glycol polyethyleneimine nanogel
Nanogels
pullulan
Pneumococcal Vaccines