{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:56:47Z","timestamp":1769619407284,"version":"3.49.0"},"reference-count":38,"publisher":"Pharmaceutical Society of Japan","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological & Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2026,1,21]]},"DOI":"10.1248\/bpb.b25-00668","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T22:09:46Z","timestamp":1768946986000},"page":"141-148","source":"Crossref","is-referenced-by-count":0,"title":["Ionic Liquids Composed of Lactic Acid and Trometamol Enhance the Oral Absorption of 10 kDa Dextran, as a Model Compound of Mid-Sized Molecules"],"prefix":"10.1248","volume":"49","author":[{"given":"Shoichiro","family":"Fukuda","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Takata","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"},{"name":"Innovative Research Center for Drug Delivery System, Institute of Biomedical Sciences, Tokushima University, 2\u201324 Shinkura-cho, Tokushima 770\u20138501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haruka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nakae","sequence":"additional","affiliation":[{"name":"MEDRx Co., Ltd., 431\u20137 Nishiyama, Higashikagawa, Kagawa 769\u20132712, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noboru","family":"Tatsumi","sequence":"additional","affiliation":[{"name":"MEDRx Co., Ltd., 431\u20137 Nishiyama, Higashikagawa, Kagawa 769\u20132712, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetoshi","family":"Hamamoto","sequence":"additional","affiliation":[{"name":"MEDRx Co., Ltd., 431\u20137 Nishiyama, Higashikagawa, Kagawa 769\u20132712, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shingo","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"},{"name":"Innovative Research Center for Drug Delivery System, Institute of Biomedical Sciences, Tokushima University, 2\u201324 Shinkura-cho, Tokushima 770\u20138501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuhiro","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1\u201378\u20131 Sho-machi, Tokushima 770\u20138505, Japan"},{"name":"Innovative Research Center for Drug Delivery System, Institute of Biomedical Sciences, Tokushima University, 2\u201324 Shinkura-cho, Tokushima 770\u20138501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"163","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Al Musaimi O, AlShaer D, de la Torre BG, Albericio F. 2024 FDA TIDES (peptides and oligonucleotides) harvest. Pharmaceuticals<\/i>, 18<\/b>, 291 (2025).","DOI":"10.3390\/ph18030291"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Xiao W, Jiang W, Chen Z, Huang Y, Mao J, Zheng W, Hu Y, Shi J. Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines. Signal Transduct. Target. Ther.<\/i>, 10<\/b>, 74 (2025).","DOI":"10.1038\/s41392-024-02107-5"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Fu AZ, Qiu Y, Radican L. Impact of fear of insulin or fear of injection on treatment outcomes of patients with diabetes. Curr. Med. Res. Opin.<\/i>, 25<\/b>, 1413\u20131420 (2009).","DOI":"10.1185\/03007990902905724"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Brown TD, Whitehead KA, Mitragotri S. Materials for oral delivery of proteins and peptides. Nat. Rev. Mater.<\/i>, 5<\/b>, 127\u2013148 (2020).","DOI":"10.1038\/s41578-019-0156-6"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Devadasu VR DP, Maheshwari R, Sharma P, Tekade RK. Chapter 5\u2014Physicochemical, pharmaceutical, and biological considerations in git absorption of drugs. Dosage Form Design Considerations<\/i>, 2018<\/b>, 149\u2013178 (2018).","DOI":"10.1016\/B978-0-12-814423-7.00005-8"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Hamman JH, Enslin GM, Kotz\u00e9 AF. Oral delivery of peptide drugs: barriers and developments. BioDrugs<\/i>, 19<\/b>, 165\u2013177 (2005).","DOI":"10.2165\/00063030-200519030-00003"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Tyagi P, Pechenov S, Anand Subramony J. Oral peptide delivery: Translational challenges due to physiological effects. J. Control. Release<\/i>, 287<\/b>, 167\u2013176 (2018).","DOI":"10.1016\/j.jconrel.2018.08.032"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Buckley ST, Baekdal TA, Vegge A, et al<\/i>. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci. Transl. Med.<\/i>, 10<\/b>, eaar7047 (2018).","DOI":"10.1126\/scitranslmed.aar7047"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Brayden DJ, Maher S, Bahar B, Walsh E. Sodium caprate-induced increases in intestinal permeability and epithelial damage are prevented by misoprostol. Eur. J. Pharm. Biopharm.<\/i>, 94<\/b>, 194\u2013206 (2015).","DOI":"10.1016\/j.ejpb.2015.05.013"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Twarog C, Liu K, O\u2019Brien PJ, Dawson KA, Fattal E, Illel B, Brayden DJ. A head-to-head Caco-2 assay comparison of the mechanisms of action of the intestinal permeation enhancers: SNAC and sodium caprate (C10<\/sub>). Eur. J. Pharm. Biopharm.<\/i>, 152<\/b>, 95\u2013107 (2020).","DOI":"10.1016\/j.ejpb.2020.04.023"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Aroda VR, Blonde L, Pratley RE. A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev. Endocr. Metab. Disord.<\/i>, 23<\/b>, 979\u2013994 (2022).","DOI":"10.1007\/s11154-022-09735-8"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Solis-Herrera C, Kane MP, Triplitt C. Current understanding of sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate (SNAC) as an absorption enhancer: the oral semaglutide experience. Clin. Diabetes<\/i>, 42<\/b>, 74\u201386 (2024).","DOI":"10.2337\/cd22-0118"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Dan N, Samanta K, Almoazen H. An update on pharmaceutical strategies for oral delivery of therapeutic peptides and proteins in adults and pediatrics. Children<\/i>, 7<\/b>, 307 (2020).","DOI":"10.3390\/children7120307"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Zhao K, Li S, Li W, Yu L, Duan X, Han J, Wang X, Jin Z. Quaternized chitosan nanoparticles loaded with the combined attenuated live vaccine against Newcastle disease and infectious bronchitis elicit immune response in chicken after intranasal administration. Drug Deliv.<\/i>, 24<\/b>, 1574\u20131586 (2017).","DOI":"10.1080\/10717544.2017.1388450"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Makhlof A, Fujimoto S, Tozuka Y, Takeuchi H. In vitro<\/i> and in vivo<\/i> evaluation of WGA-carbopol modified liposomes as carriers for oral peptide delivery. Eur. J. Pharm. Biopharm.<\/i>, 77<\/b>, 216\u2013224 (2011).","DOI":"10.1016\/j.ejpb.2010.12.008"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Yin L, Ding J, He C, Cui L, Tang C, Yin C. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery. Biomaterials<\/i>, 30<\/b>, 5691\u20135700 (2009).","DOI":"10.1016\/j.biomaterials.2009.06.055"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Ghadi R, Dand N. BCS class IV drugs: Highly notorious candidates for formulation development. J. Control. Release<\/i>, 248<\/b>, 71\u201395 (2017).","DOI":"10.1016\/j.jconrel.2017.01.014"},{"key":"18","unstructured":"18) Walden P. Molecular weights and electrical conductivity of several fused salts. Bull. Acad. Sci. St.-Petersbourg<\/i>, 8<\/b>, 405\u2013422 (1914)."},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Jiang A, Nidamanuri N, Zhang C, Li Z. Ionic-liquid-assisted one-step synthesis of CoO nanosheets as electrocatalysts for oxygen evolution reaction. ACS Omega<\/i>, 3, 10092\u201310098 (2018).","DOI":"10.1021\/acsomega.8b01394"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Wasserscheid P, Keim W. Ionic liquids-new \u201csolutions\u201d for transition metal catalysis. Angew. Chem. Int. Ed.<\/i>, 39<\/b>, 3772\u20133789 (2000).","DOI":"10.1002\/1521-3773(20001103)39:21<3772::AID-ANIE3772>3.0.CO;2-5"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Rogers RD, Seddon KR. Chemistry. Ionic liquids\u2014solvents of the future? Science<\/i>, 302<\/b>, 792\u2013793 (2003).","DOI":"10.1126\/science.1090313"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Li X, Ma N, Zhang L, Ling G, Zhang P. Applications of choline-based ionic liquids in drug delivery. Int. J. Pharm.<\/i>, 612<\/b>, 121366 (2022).","DOI":"10.1016\/j.ijpharm.2021.121366"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Banerjee A, Ibsen K, Iwao Y, Zakrewsky M, Mitragotri S. Transdermal protein delivery using choline and geranate (CAGE) deep eutectic solvent. Adv. Healthc. Mater.<\/i>, 6<\/b>, 1601411 (2017).","DOI":"10.1002\/adhm.201601411"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Tanner EEL, Ibsen KN, Mitragotri S. Transdermal insulin delivery using choline-based ionic liquids (CAGE). J. Control. Release<\/i>, 286<\/b>, 137\u2013144 (2018).","DOI":"10.1016\/j.jconrel.2018.07.029"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Shimizu T, Matsuzaki T, Fukuda S, Yoshioka C, Shimazaki Y, Takese S, Yamanaka K, Nakae T, Ishibashi M, Hamamoto H, Ando H, Ishima Y, Ishida T. Ionic liquid-based transcutaneous peptide antitumor vaccine: therapeutic effect in a mouse tumor model. AAPS J.<\/i>, 25<\/b>, 27 (2023).","DOI":"10.1208\/s12248-023-00790-w"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Banerjee A, Ibsen K, Brown T, Chen R, Agatemor C, Mitragotri S. Ionic liquids for oral insulin delivery. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 115<\/b>, 7296\u20137301 (2018).","DOI":"10.1073\/pnas.1722338115"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Francisco M, van den Bruinhorst A, Kroon MC. Low-transition-temperature mixtures (LTTMs): a new generation of designer solvents. Angew. Chem. Int. Ed.<\/i>, 52<\/b>, 3074\u20133085 (2013).","DOI":"10.1002\/anie.201207548"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Banerjee A, Ibsen K, Brown T, Chen R, Agatemor C, Mitragotri S. Reply to rogers and gurau: definitions of ionic liquids and deep eutectic solvents. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 115<\/b>, E11000\u2013E11001 (2018).","DOI":"10.1073\/pnas.1815526115"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Rogers RD, Gurau G. Is \u201ccholine and geranate\u201d an ionic liquid or deep eutectic solvent system? Proc. Natl. Acad. Sci. U.S.A.<\/i>, 115<\/b>, E10999 (2018).","DOI":"10.1073\/pnas.1814976115"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Emma L, Smith APA, Karl S. Ryder. Deep eutectic solvents (DESs) and their applications. Chem. Rev.<\/i>, 114<\/b>, 11060\u201311082 (2014).","DOI":"10.1021\/cr300162p"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Moshikur RM, Carrier RL, Moniruzzaman M, Goto M. Recent advances in biocompatible ionic liquids in drug formulation and delivery. Pharmaceutics<\/i>, 15<\/b>, 1179 (2023).","DOI":"10.3390\/pharmaceutics15041179"},{"key":"32","unstructured":"32) Additives JFWECoF. \u201cWHO FOOD ADDITIVES SERIES NO. 5.\u201d <https:\/\/www.inchem.org\/documents\/jecfa\/jecmono\/v05je01.htm>."},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Vallet T, Michelon H, Orlu M, Jani Y, Leglise P, Laribe-Caget S, Piccoli M, Le Fur A, Liu F, Ruiz F, Boudy V. Acceptability in the older population: the importance of an appropriate tablet size. Pharmaceutics<\/i>, 12<\/b>, 746 (2020).","DOI":"10.3390\/pharmaceutics12080746"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Chen G, Kang W, Li W, Chen S, Gao Y. Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies. Theranostics<\/i>, 12<\/b>, 1419\u20131439 (2022).","DOI":"10.7150\/thno.61747"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Mitragotri S. Choline geranate (CAGE): a multifaceted ionic liquid for drug delivery. J. Control. Release<\/i>, 376<\/b>, 593\u2013600 (2024).","DOI":"10.1016\/j.jconrel.2024.10.034"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Vaidya A, Mitragotri S. Ionic liquid-mediated delivery of insulin to buccal mucosa. J. Control. Release<\/i>, 327<\/b>, 26\u201334 (2020).","DOI":"10.1016\/j.jconrel.2020.07.037"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Yang M, Wu H, Lian Y, Li X, Ren Y, Lai F, Zhao G. Using ionic liquids in whole-cell biocatalysis for the nucleoside acylation. Microb. Cell Fact.<\/i>, 13<\/b>, 143 (2014).","DOI":"10.1186\/PREACCEPT-2071959743130788"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Sivapragasam M, Moniruzzaman M, Goto M. Recent advances in exploiting ionic liquids for biomolecules: solubility, stability and applications. Biotechnol. J.<\/i>, 11<\/b>, 1000\u20131013 (2016).","DOI":"10.1002\/biot.201500603"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00668\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T03:28:47Z","timestamp":1769225327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00668\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b25-00668","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"article-number":"b25-00668"}}