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dc.contributor.authorUlapane, Kavisha R.
dc.contributor.authorKopec, Brian M.
dc.contributor.authorSiahaan, Teruna J.
dc.identifier.citationUlapane, K. R., Kopec, B. M., & Siahaan, T. J. (2019). In Vivo Brain Delivery and Brain Deposition of Proteins with Various Sizes. Molecular pharmaceutics, 16(12), 4878–4889.
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
dc.description.abstractIt is very challenging to develop protein drugs for the treatment of brain diseases; this is due to the difficulty in delivering them into the brain because of the blood–brain barrier (BBB). Thus, alternative delivery methods need further exploration for brain delivery of proteins to diagnose and treat brain diseases. Previously, ADTC5 and HAV6 peptides have been shown to enhance the in vivo brain delivery of small- and medium-size molecules across the BBB. This study was carried out to evaluate the ability of ADTC5 and HAV6 peptides to enhance delivery of proteins of various sizes, such as 15 kDa lysozyme, 65 kDa albumin, 150 kDa IgG mAb, and 220 kDa fibronectin, into the brains of C57BL/6 mice. Each protein was labeled with IRdye800CW, and a quantitative method using near IR fluorescence (NIRF) imaging was developed to determine the amount of protein delivered into the brain. ADTC5 peptide significantly enhanced brain delivery of lysozyme, albumin, and IgG mAb but not fibronectin compared to controls. In contrast, HAV6 peptide significantly enhanced the brain delivery of lysozyme but not albumin and IgG mAb. Thus, there is a cutoff size of proteins that can be delivered by each peptide. The distribution of delivered protein in other organs such as liver, spleen, lung, kidney, and heart could be influenced by HAV6 and ADTC5. In summary, ADTC5 is a better BBB modulator than HAV6 in delivering various sizes of proteins into the brain, and the size of the protein affects its brain delivery.en_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsCopyright © 2019 American Chemical Society.en_US
dc.subjectBlood-brain barrieren_US
dc.subjectCadherin peptidesen_US
dc.subjectProtein brain deliveryen_US
dc.subjectParacellular pathwayen_US
dc.subjectIn vivo brain deliveryen_US
dc.titleIn Vivo Brain Delivery and Brain Deposition of Proteins with Various Sizesen_US
kusw.kuauthorUlapane, Kavisha R.
kusw.kuauthorKopec, Brian M.
kusw.kuauthorSiahaan, Teruna J.
kusw.kudepartmentPharmaceutical Chemistryen_US
kusw.oanotesPer Sherpa Romeo 12/01/2021:

Molecular Pharmaceutics [Open panel below]Publication Information TitleMolecular Pharmaceutics [English] ISSNs Print: 1543-8384 Electronic: 1543-8392 URL PublishersAmerican Chemical Society [Society Publisher] [Open panel below]Publisher Policy Open Access pathways permitted by this journal's policy are listed below by article version. Click on a pathway for a more detailed view.

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NoneCC BYPMC PMC, Funder Designated Location, Journal Website Published Version [pathway b]

12mCC BY Institutional Repository, PMC, Author's Homepage, +1 Accepted Version 12m Non-Commercial Institutional Repository, Non-Commercial Subject Repository, +3 PrerequisitesIf Required by Funder, If Required by Institution Embargo12 Months Location Author's Homepage Institutional Website Non-Commercial Institutional Repository Non-Commercial Subject Repository Preprint Repository Conditions Must be accompanied by set statement (see policy) Must link to publisher version NotesIf mandated to deposit before 12 months, the author must obtain a waiver from their Institution/Funding agency or use AuthorChoice
dc.identifier.orcid 0000-0001-7250-0627en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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