Oral Delivery of Bioencapsulated Proteins Across Blood–Brain and Blood–Retinal Barriers

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dc.contributor.authorKohli, Neha
dc.contributor.authorWesterveld, Donevan R.
dc.contributor.authorAyache, Alexandra C.
dc.contributor.authorVerma, Amrisha
dc.contributor.authorShil, Pollob
dc.contributor.authorPrasad, Tuhina
dc.contributor.authorZhu, Ping
dc.contributor.authorChan, Sic L.
dc.contributor.authorLi, Qiuhong
dc.contributor.authorDaniell, Henry
dc.date2023-05-17T23:06:44.000
dc.date.accessioned2023-05-22T13:14:07Z
dc.date.available2023-05-22T13:14:07Z
dc.date.issued2014-01-07
dc.date.submitted2019-11-21T10:42:52-08:00
dc.description.abstractDelivering neurotherapeutics to target brain-associated diseases is a major challenge. Therefore, we investigated oral delivery of green fluorescence protein (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant cells) to the brain and retinae of triple transgenic Alzheimer's disease (3×TgAD) mice, across the blood–brain barriers (BBB) and blood–retinal barriers (BRB). Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not with GFP alone. Oral delivery of CTB-MBP in healthy and 3×TgAD mice shows increased MBP levels in different regions of the brain, crossing intact BBB. Thioflavin S–stained amyloid plaque intensity was reduced up to 60% by CTB-MBP incubation with human AD and 3×TgAD mice brain sections ex vivo. Amyloid loads were reduced in vivo by 70% in hippocampus and cortex brain regions of 3×TgAD mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of insoluble amyloid β 42 (Aβ42) to soluble fractions. CTB-MBP oral delivery reduced Aβ42 accumulation in retinae and prevented loss of retinal ganglion cells in 3×TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and stabilized it during long-term storage in capsules, facilitating low-cost oral delivery of therapeutic proteins across the BBB and BRB.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/8991
dc.legacy.articleid1167
dc.legacy.fields10.1038/mt.2013.273
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1167&context=dental_papers&unstamped=1
dc.rights<p>© <2014>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</a></p>
dc.source.beginpage535
dc.source.endpage546
dc.source.issue271
dc.source.issue3
dc.source.journalDepartmental Papers (Dental)
dc.source.journaltitleMolecular Therapy
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume22
dc.subject.otherDentistry
dc.titleOral Delivery of Bioencapsulated Proteins Across Blood–Brain and Blood–Retinal Barriers
dc.typeArticle
digcom.contributor.authorKohli, Neha
digcom.contributor.authorWesterveld, Donevan R.
digcom.contributor.authorAyache, Alexandra C.
digcom.contributor.authorVerma, Amrisha
digcom.contributor.authorShil, Pollob
digcom.contributor.authorPrasad, Tuhina
digcom.contributor.authorZhu, Ping
digcom.contributor.authorChan, Sic L.
digcom.contributor.authorLi, Qiuhong
digcom.contributor.authorDaniell, Henry
digcom.identifierdental_papers/271
digcom.identifier.contextkey15841125
digcom.identifier.submissionpathdental_papers/271
digcom.typearticle
dspace.entity.typePublication
upenn.schoolDepartmentCenterDepartmental Papers (Dental)
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