{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:14:12Z","timestamp":1787170452543,"version":"build-2736575974"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cyclodextrins are increasingly used therapeutically. For example, 2-hydroxypropyl-\u00df-cyclodextrin (kleptose) is used for the treatment of Niemann\u2013Pick disease. Kleptose crosses the blood\u2013brain barrier poorly, in part because of a central nervous system (CNS)-to-blood (efflux) transporter, and so is administered by the intrathecal (IT) route in the treatment of Niemann\u2013Pick disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we evaluated the uptake and distribution of kleptose by the brain and spinal cord after intranasal (IN) or IT delivery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>Kleptose distributed to all regions of the brain and spinal cord after IN administration, with only 3.27% of the administered dose entering the bloodstream. Intrathecal delivery produced levels in the whole brain about 40 times higher than intranasal administration and about 20 times higher than previously found after intravenous administration. About 70\u201390% of the IT dose rapidly entered the bloodstream, in part because of the previously described efflux transporter. The uptake by CNS after IN and IT was both non-saturable. The uptake by the olfactory bulb, hypothalamus and pons-medulla was favoured by all routes of administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Kleptose was taken up by all regions of the CNS after either IN or IT administration, but IN administration resulted in only a fraction of the uptake of the IT route.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgac001","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T23:33:40Z","timestamp":1644017620000},"page":"1152-1159","source":"Crossref","is-referenced-by-count":5,"title":["Brain uptake and distribution patterns of 2-hydroxypropyl-\u00df-cyclodextrin after intrathecal and intranasal administration"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-3619","authenticated-orcid":false,"given":"William A","family":"Banks","sequence":"first","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System , Seattle, WA ,","place":["USA"]},{"name":"Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pericles","family":"Calias","sequence":"additional","affiliation":[{"name":"Educational Trainers and Consultants , Melrose, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim M","family":"Hansen","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System , Seattle, WA ,","place":["USA"]},{"name":"Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin M","family":"Bullock","sequence":"additional","affiliation":[{"name":"Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System , Seattle, WA ,","place":["USA"]},{"name":"Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kory","family":"Engelke","sequence":"additional","affiliation":[{"name":"The Engelke Group , Keymar, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"2024103012174280500_CIT0001","first-page":"1023","article-title":"Cyclodextrin-based pharmaceutics: past, present, and future","volume-title":"Nat Rev Drug Discov","author":"Davis","year":"2004"},{"key":"2024103012174280500_CIT0002","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2174\/138920310791233387","article-title":"Cyclodextrins: an overview of the complexation of pharmaceutical proteins","volume":"11","author":"Varca","year":"2010","journal-title":"Curr Protein Pept Sci"},{"key":"2024103012174280500_CIT0003","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1111\/j.2042-7158.2010.01030.x","article-title":"Pharmaceutical applications of cyclodextrins: basic science and product development","volume":"62","author":"Loftsson","year":"2010","journal-title":"J Pharm Pharmacol"},{"key":"2024103012174280500_CIT0004","first-page":"1107","article-title":"Absorption enhancers for nasal drug delivery","volume-title":"Clin Pharmacokinet","author":"Davis","year":"2003"},{"key":"2024103012174280500_CIT0005","first-page":"41","article-title":"Cyclodextrins in nasal drug delivery","volume-title":"Adv Drug Deliv Rev","author":"Merkus","year":"1999"},{"key":"2024103012174280500_CIT0006","first-page":"101","article-title":"Cyclodextrins in peptide and protein delivery","volume-title":"Adv Drug Deliv Rev","author":"Irie","year":"1999"},{"key":"2024103012174280500_CIT0007","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/nm919","article-title":"Glucagon-like peptide-1 receptor is involved in learning and neuroprotection","volume":"9","author":"During","year":"2003","journal-title":"Nat Med"},{"key":"2024103012174280500_CIT0008","first-page":"46","article-title":"Bypassing the blood-brain barrier to deliver therapeutic agents to the brain and spinal cord","volume":"2","author":"Frey","year":"2002","journal-title":"Drug Deliv Technol"},{"key":"2024103012174280500_CIT0009","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1124\/jpet.107.132381","article-title":"Delivery of galanin-like peptide to the brain: targeting with intranasal delivery and cyclodextrins","volume":"325","author":"Nonaka","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"2024103012174280500_CIT0010","first-page":"168","article-title":"Intranasal administration of PACAP: uptake by brain and regional brain targeting with cyclodextrins","volume-title":"Peptides","author":"Nonaka","year":"2012"},{"key":"2024103012174280500_CIT0011","first-page":"6231","article-title":"2-Hydroxypropyl-Beta-cyclodextrins and the blood-brain barrier: considerations for Niemann-Pick disease type C1","volume-title":"Curr Pharm Des","author":"Calias","year":"2017"},{"key":"2024103012174280500_CIT0012","first-page":"e6951","article-title":"Chronic cyclodextrin treatment of murine Niemann-Pick C disease ameliorates neuronal cholesterol and glycosphingolipid storage and disease progression","volume-title":"PLoS One","author":"Davidson","year":"2009"},{"key":"2024103012174280500_CIT0013","first-page":"121","article-title":"Modest blood-brain barrier permeability of the cyclodextrin kleptose: modification by efflux and luminal surface binding","volume-title":"J Pharmacol Exp Ther","author":"Banks","year":"2019"},{"key":"2024103012174280500_CIT0014","first-page":"2377","article-title":"Reversal of defective lysosomal transport in NPS disease ameliorates liver dysfunction and neurodegneration in the npc1\u2212\/\u2212 mouse","volume-title":"Proc Natl Acad Sci USA","author":"Liu","year":"2009"},{"key":"2024103012174280500_CIT0015","first-page":"391","article-title":"Effects of intracerebroven\u00adtricular administration of 2-hydroxypropyl-beta-cyclodextrin in a patient with Niemann-Pick type C disease","volume-title":"Mol Genet Metab Rep","author":"Matsuo","year":"2014"},{"key":"2024103012174280500_CIT0016","first-page":"76","article-title":"Effects of cyclodextrin in two patients with Niemann-Pick type C disease","volume-title":"Mol Genet Metab","author":"Matsuo","year":"2013"},{"key":"2024103012174280500_CIT0017","first-page":"491","article-title":"Cyclodextrin alleviates neuronal storage of cholesterol in Niemann-Pick C disease without evidence of detectable blood-brain barrier permeability","volume-title":"J Inherit Metab Dis","author":"Pontikis","year":"2013"},{"key":"2024103012174280500_CIT0018","first-page":"469","article-title":"Brain uptake of glucagon-like peptide-1 antagonist exendin(9-39) after intranasal administration","volume-title":"J Pharmacol Exp Ther","author":"Banks","year":"2004"},{"key":"2024103012174280500_CIT0019","first-page":"1326","article-title":"Intranasal insulin improves memory in humans","volume-title":"Psychoneuroendocrinology","author":"Benedict","year":"2004"},{"key":"2024103012174280500_CIT0020","first-page":"2086","article-title":"Intranasal leptin: blood-brain barrier bypass (BBBB) for obesity?","volume-title":"Endocrinology","author":"Kastin","year":"2006"},{"key":"2024103012174280500_CIT0021","first-page":"614","article-title":"Intranasal delivery of biologics to the central nervous system","volume-title":"Adv Drug Deliv Rev","author":"Lochhead","year":"2012"},{"key":"2024103012174280500_CIT0022","first-page":"715","article-title":"Central nervous system delivery of intranasal insulin: mechanisms of uptake and effects on cognition","volume-title":"J Alzheimers Dis","author":"Salameh","year":"2015"},{"key":"2024103012174280500_CIT0023","volume-title":"The Concept of a Blood-Brain Barrier","author":"Bradbury","year":"1979"},{"key":"2024103012174280500_CIT0024","first-page":"R818","article-title":"Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat","volume-title":"Am J Physiol","author":"Boulton","year":"1999"},{"key":"2024103012174280500_CIT0025","first-page":"489","volume-title":"Physiology of the CSF and Blood-Brain Barriers","author":"Davson","year":"1996"},{"key":"2024103012174280500_CIT0026","first-page":"e30341","article-title":"CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: implications for neurological outcomes of lysosomal storage disorder","volume-title":"PLoS One","author":"Calias","year":"2012"},{"key":"2024103012174280500_CIT0027","first-page":"81","article-title":"The impact of efflux transporters in the brain on the development of drugs for CNS disorders","volume-title":"Clin Pharmacokinet","author":"Taylor","year":"2002"},{"key":"2024103012174280500_CIT0028","first-page":"1295","article-title":"ABC transporters and the blood-brain barrier","volume-title":"Curr Pharm Des","author":"Begley","year":"2004"},{"key":"2024103012174280500_CIT0029","first-page":"236","article-title":"P-glycoprotein inhibition by membrane cholesterol modulation","volume-title":"Eur J Pharm Sci","author":"Fenyvesi","year":"2008"},{"key":"2024103012174280500_CIT0030","first-page":"544","article-title":"Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug\/cyclodextrin complexes","volume-title":"J Pharm Pharmacol","author":"Loftsson","year":"2016"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/74\/8\/1152\/60218789\/rgac001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/74\/8\/1152\/60218789\/rgac001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:06:23Z","timestamp":1730293583000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/74\/8\/1152\/6590334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,1]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,1]]},"published-print":{"date-parts":[[2022,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgac001","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,8,1]]},"published":{"date-parts":[[2022,8,1]]}}}