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dc.contributor.authorBleier, Benjamin
dc.contributor.authorKohman, Richie E.
dc.contributor.authorFeldman, Rachel Elizabeth
dc.contributor.authorRamanlal, Shreshtha
dc.contributor.authorHan, Xue
dc.date.accessioned2013-10-17T20:02:46Z
dc.date.issued2013
dc.identifier.citationBleier, Benjamin S., Richie E. Kohman, Rachel E. Feldman, Shreshtha Ramanlal, and Xue Han. 2013. Permeabilization of the blood-brain barrier via mucosal engrafting: implications for drug delivery to the brain. PLoS ONE 8(4): e61694.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181048
dc.description.abstractUtilization of neuropharmaceuticals for central nervous system(CNS) disease is highly limited due to the blood-brain barrier(BBB) which restricts molecules larger than 500Da from reaching the CNS. The development of a reliable method to bypass the BBB would represent an enormous advance in neuropharmacology enabling the use of many potential disease modifying therapies. Previous attempts such as transcranial catheter implantation have proven to be temporary and associated with multiple complications. Here we describe a novel method of creating a semipermeable window in the BBB using purely autologous tissues to allow for high molecular weight(HMW) drug delivery to the CNS. This approach is inspired by recent advances in human endoscopic transnasal skull base surgical techniques and involves engrafting semipermeable nasal mucosa within a surgical defect in the BBB. The mucosal graft thereby creates a permanent transmucosal conduit for drugs to access the CNS. The main objective of this study was to develop a murine model of this technique and use it to evaluate transmucosal permeability for the purpose of direct drug delivery to the brain. Using this model we demonstrate that mucosal grafts allow for the transport of molecules up to 500 kDa directly to the brain in both a time and molecular weight dependent fashion. Markers up to 40 kDa were found within the striatum suggesting a potential role for this technique in the treatment of Parkinson’s disease. This proof of principle study demonstrates that mucosal engrafting represents the first permanent and stable method of bypassing the BBB thereby providing a pathway for HMW therapeutics directly into the CNS.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0061694en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634848/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectModel Organismsen_US
dc.subjectNeuroscienceen_US
dc.subjectNeuroanatomyen_US
dc.subjectMedicineen_US
dc.subjectDrugs and Devicesen_US
dc.subjectPharmacokineticsen_US
dc.subjectDrug Absorptionen_US
dc.subjectMedical Devicesen_US
dc.subjectNeuropharmacologyen_US
dc.subjectNeurologyen_US
dc.subjectNeurodegenerative Diseasesen_US
dc.subjectParkinson Diseaseen_US
dc.subjectSurgeryen_US
dc.subjectMinimally Invasive Surgeryen_US
dc.subjectEndoscopyen_US
dc.subjectHead and Neck Surgeryen_US
dc.subjectNeurosurgeryen_US
dc.titlePermeabilization of the Blood-Brain Barrier via Mucosal Engrafting: Implications for Drug Delivery to the Brainen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorBleier, Benjamin
dc.date.available2013-10-17T20:02:46Z
dc.identifier.doi10.1371/journal.pone.0061694*
dash.contributor.affiliatedFeldman, Rachel Elizabeth
dash.contributor.affiliatedBleier, Benjamin


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