{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:51:11Z","timestamp":1780087871339,"version":"3.54.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T00:00:00Z","timestamp":1551830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann-Pick disease Type C (NPC) is a rare lysosomal storage disease characterized by the dysfunction of intracellular cholesterol trafficking with progressive neurodegeneration and hepatomegaly. We evaluated the potential of 6-O-\u03b1-maltosyl-\u03b2-cyclodextrin (G2-\u03b2-CD) as a drug candidate against NPC. The physicochemical properties of G2-\u03b2-CD as an injectable agent were assessed, and molecular interactions between G2-\u03b2-CD and free cholesterol were studied by solubility analysis and two-dimensional proton nuclear magnetic resonance spectroscopy. The efficacy of G2-\u03b2-CD against NPC was evaluated using Npc1 deficient Chinese hamster ovary (CHO) cells and Npc1 deficient mice. G2-\u03b2-CD in aqueous solution showed relatively low viscosity and surface activity; characteristics suitable for developing injectable formulations. G2-\u03b2-CD formed higher-order inclusion complexes with free cholesterol. G2-\u03b2-CD attenuated dysfunction of intercellular cholesterol trafficking and lysosome volume in Npc1 deficient CHO cells in a concentration dependent manner. Weekly subcutaneous injections of G2-\u03b2-CD (2.9 mmol\/kg) ameliorated abnormal cholesterol metabolism, hepatocytomegaly, and elevated serum transaminases in Npc1 deficient mice. In addition, a single cerebroventricular injection of G2-\u03b2-CD (21.4 \u03bcmol\/kg) prevented Purkinje cell loss in the cerebellum, body weight loss, and motor dysfunction in Npc1 deficient mice. In summary, G2-\u03b2-CD possesses characteristics favorable for injectable formulations and has therapeutic potential against in vitro and in vivo NPC models.<\/jats:p>","DOI":"10.3390\/ijms20051152","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T10:52:22Z","timestamp":1551955942000},"page":"1152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["In Vitro and In Vivo Evaluation of 6-O-\u03b1-Maltosyl-\u03b2-Cyclodextrin as a Potential Therapeutic Agent Against Niemann-Pick Disease Type C"],"prefix":"10.3390","volume":"20","author":[{"given":"Nushrat","family":"Yasmin","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"},{"name":"Program for Leading Graduate Schools \u201cHIGO (Health life science: Interdisciplinary and Glocal Oriented) Program\u201d, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-4469","authenticated-orcid":false,"given":"Yoichi","family":"Ishitsuka","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madoka","family":"Fukaura","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"},{"name":"Program for Leading Graduate Schools \u201cHIGO (Health life science: Interdisciplinary and Glocal Oriented) Program\u201d, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-2919","authenticated-orcid":false,"given":"Yusei","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-7721","authenticated-orcid":false,"given":"Yuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-651X","authenticated-orcid":false,"given":"Toru","family":"Takeo","sequence":"additional","affiliation":[{"name":"Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Nakagata","sequence":"additional","affiliation":[{"name":"Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Motoyama","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taishi","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyo","family":"Okada","sequence":"additional","affiliation":[{"name":"Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women\u2019s University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Iohara","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Pharmaceutics, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, 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