{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:00:51Z","timestamp":1785186051108,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Sasakawa Scientific Research Grant","award":["2018-3039"],"award-info":[{"award-number":["2018-3039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We have recently reported Catalytides (Catalytic peptides) JAL-TA9 (YKGSGFRMI) and ANA-TA9 (SKGQAYRMI), which are the first Catalytides found to cleave A\u03b242. Although the Catalytides must be delivered to the brain parenchyma to treat Alzheimer\u2019s disease, the blood\u2013brain barrier (BBB) limits their entry into the brain from the systemic circulation. To avoid the BBB, the direct route from the nasal cavity to the brain was used in this study. The animal studies using rats and mice clarified that the plasma clearance of ANA-TA9 was more rapid than in vitro degradation in the plasma, whole blood, and the cerebrospinal fluid (CSF). The brain concentrations of ANA-TA9 were higher after nasal administration than those after intraperitoneal administration, despite a much lower plasma concentration after nasal administration, suggesting the direct delivery of ANA-TA9 to the brain from the nasal cavity. Similar findings were observed for its transport to CSF after nasal and intravenous administration. The concentration of ANA-TA9 in the olfactory bulb reached the peak at 5 min, whereas those in the frontal and occipital brains was 30 min, suggesting the sequential backward translocation of ANA-TA9 in the brain. In conclusion, ANA-TA9 was efficiently delivered to the brain by nasal application, as compared to other routes.<\/jats:p>","DOI":"10.3390\/pharmaceutics13101673","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T21:48:39Z","timestamp":1634161719000},"page":"1673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Direct Delivery of ANA-TA9, a Peptide Capable of A\u03b2 Hydrolysis, to the Brain by Intranasal Administration"],"prefix":"10.3390","volume":"13","author":[{"given":"Yusuke","family":"Hatakawa","sequence":"first","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba, Sendai 980-8578, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-Machi 4-19-1 Higashinada, Kobe, Hyogo 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4397-4353","authenticated-orcid":false,"given":"Tomoyuki","family":"Furubayashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-Machi 4-19-1 Higashinada, Kobe, Hyogo 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Nakamura","sequence":"additional","affiliation":[{"name":"O-Force Co., Ltd., 3454 Irino Kuroshio-Cho, Hata-Gun, Kochi 789-1931, Japan"},{"name":"Laboratory of Pharmacology, School of Medicine, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomi","family":"Konishi","sequence":"additional","affiliation":[{"name":"Department of Integrative Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-Cho, Hirakata, Osaka 573-0101, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Akizawa","sequence":"additional","affiliation":[{"name":"O-Force Co., Ltd., 3454 Irino Kuroshio-Cho, Hata-Gun, Kochi 789-1931, Japan"},{"name":"Laboratory of Pharmacology, School of Medicine, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Sakane","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyamakita-Machi 4-19-1 Higashinada, Kobe, Hyogo 658-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13195-017-0297-z","article-title":"Alzheimer\u2018s disease prevention: From risk factors to early intervention","volume":"9","author":"Minguillon","year":"2017","journal-title":"Alzheimers Res. 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