Modulation of Intercellular Junctions by Cyclic-ADT Peptides as a Method to Reversibly Increase Blood-Brain Barrier Permeability
dc.contributor.author | Laksitorini, Marlyn D. | |
dc.contributor.author | Kiptoo, Paul | |
dc.contributor.author | On, Ngoc | |
dc.contributor.author | Thliveris, James A. | |
dc.contributor.author | Miller, Donald W. | |
dc.contributor.author | Siahaan, Teruna J. | |
dc.date.accessioned | 2017-04-25T19:30:35Z | |
dc.date.available | 2017-04-25T19:30:35Z | |
dc.date.issued | 2015-03 | |
dc.identifier.citation | Laksitorini, M. D., Kiptoo, P. K., On, N. H., Thliveris, J. A., Miller, D. W., & Siahaan, T. J. (2015). Modulation of Intercellular Junctions by Cyclic-ADT Peptides as a Method to Reversibly Increase Blood-Brain Barrier Permeability. Journal of Pharmaceutical Sciences, 104(3), 1065–1075. http://doi.org/10.1002/jps.24309 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23773 | |
dc.description.abstract | It is challenging to deliver molecules to the brain for diagnosis and treatment of brain diseases. This is primarily due to the presence of the blood-brain barrier (BBB), which restricts the entry of many molecules into the brain. In this study, cyclic ADT peptides (ADTC1, ADTC5, and ADTC6) have been shown to modify the BBB to enhance the delivery of marker molecules (e.g., 14C-mannitol, Gd-DTPA) to the brain via the paracellular pathways of the BBB. The hypothesis is that these peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells forming the BBB to increase paracellular drug permeation. In vitro studies indicated that ADTC5 had the best profile to inhibit adherens junction resealing in MDCK cell monolayers in a concentration-dependent manner (IC50 = 0.3 mM) with a maximal response at 0.4 mM. Under the current experimental conditions, ADTC5 improved the delivery of 14C-mannitol to the brain about twofold compared to the negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide increased in vivo delivery of Gd-DTPA to the brain of Balb/c mice when administered intravenously (i.v.). In conclusion, ADTC5 has the potential to improve delivery of diagnostic and therapeutic agents to the brain. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.title | Modulation of Intercellular Junctions by Cyclic-ADT Peptides as a Method to Reversibly Increase Blood-Brain Barrier Permeability | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Laksitorini, Marlyn D. | |
kusw.kuauthor | Kiptoo, Paul K. | |
kusw.kuauthor | Siahaan, Teruna J. | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1002/jps.24309 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4442687 | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.