{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T22:40:14Z","timestamp":1784328014147,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Quebec Ministry of Economy &amp; Innovation","award":["PSR-SIIRI no. 982"],"award-info":[{"award-number":["PSR-SIIRI no. 982"]}]},{"name":"Northern Cancer Foundation","award":["2017-2019"],"award-info":[{"award-number":["2017-2019"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJ-148531"],"award-info":[{"award-number":["PJ-148531"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-89716"],"award-info":[{"award-number":["MOP-89716"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA004443"],"award-info":[{"award-number":["DA004443"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptide therapeutics offer numerous advantages in the treatment of diseases and disorders of the central nervous system (CNS). However, they are not without limitations, especially in terms of their pharmacokinetics where their metabolic lability and low blood\u2013brain barrier penetration hinder their application. Targeted nanoparticle delivery systems are being tapped for their ability to improve the delivery of therapeutics into the brain non-invasively. We have developed a family of mannosylated glycoliposome delivery systems for targeted drug delivery applications. Herein, we demonstrate via in vivo distribution studies the potential of these glycoliposomes to improve the utility of CNS active therapeutics using dynantin, a potent and selective dynorphin peptide analogue antagonist of the kappa opioid receptor (KOR). Glycoliposomal entrapment protected dynantin against known rapid metabolic degradation and ultimately improved brain levels of the peptide by approximately 3\u20133.5-fold. Moreover, we linked this improved brain delivery with improved KOR antagonist activity by way of an approximately 30\u201340% positive modulation of striatal dopamine levels 20 min after intranasal administration. Overall, the results clearly highlight the potential of our glycoliposomes as a targeted delivery system for therapeutic agents of the CNS.<\/jats:p>","DOI":"10.3390\/ijms22157996","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T03:53:53Z","timestamp":1627358033000},"page":"7996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Improving the Utility of a Dynorphin Peptide Analogue Using Mannosylated Glycoliposomes"],"prefix":"10.3390","volume":"22","author":[{"given":"Jordan D.","family":"Lewicky","sequence":"first","affiliation":[{"name":"Health Sciences North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nya L.","family":"Fraleigh","sequence":"additional","affiliation":[{"name":"Health Sciences North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandrine L.","family":"Martel","sequence":"additional","affiliation":[{"name":"Health Sciences North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi M.-D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology and Peptide Research, Montreal Clinical Research Institute, 110 Pine Avenue W, Montreal, QC H2W 1R7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7311-869X","authenticated-orcid":false,"given":"Peter W.","family":"Schiller","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology and Peptide Research, Montreal Clinical Research Institute, 110 Pine Avenue W, Montreal, QC H2W 1R7, Canada"},{"name":"Department of Pharmacology and Physiology, University of Montreal, 2900 Boulevard \u00c9douard-Montpetit, Montreal, QC H3T 1J4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2187-7592","authenticated-orcid":false,"given":"Leila","family":"Mousavifar","sequence":"additional","affiliation":[{"name":"Glycosciences and Nanomaterial Laboratory, Department of Chemistry, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, P.O. Box 8888, Succ. Centre-ville, Montreal, QC H3C 3P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-7302","authenticated-orcid":false,"given":"Ren\u00e9","family":"Roy","sequence":"additional","affiliation":[{"name":"Glycosciences and Nanomaterial Laboratory, Department of Chemistry, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, P.O. Box 8888, Succ. Centre-ville, Montreal, QC H3C 3P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Dzung","family":"Le","sequence":"additional","affiliation":[{"name":"Centre for Addiction & Mental Health, 33 Ursula Franklin Street, Toronto, ON M5S 2S1, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, 1 King\u2019s College Circle, Toronto, ON M5S 1A8, Canada"},{"name":"Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Funk","sequence":"additional","affiliation":[{"name":"Centre for Addiction & Mental Health, 33 Ursula Franklin Street, Toronto, ON M5S 2S1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoang-Thanh","family":"Le","sequence":"additional","affiliation":[{"name":"Health Sciences North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H3, Canada"},{"name":"Medicinal Sciences Division, Northern Ontario School of Medicine, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada"},{"name":"Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada"},{"name":"Department of Biology, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1016\/j.bmc.2018.01.012","article-title":"Peptide chemistry toolbox- transforming natural peptides into peptide therapeutics","volume":"10","author":"Erak","year":"2018","journal-title":"Bioorganic Med. 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