Repository logo
 
Publication

PAMAM dendrimers: blood-brain barrier transport and neuronal uptake after focal brain ischemia

2018Journal article Restricted access
Simple item page
dc.contributor.authorSantos, Sofia D.
dc.contributor.authorXavier, Miguel
dc.contributor.authorLeite, Diana M.
dc.contributor.authorMoreira, Débora A.
dc.contributor.authorCustódio, Beatriz
dc.contributor.authorTorrado, Marília
dc.contributor.authorCastro, Rita
dc.contributor.authorLeiro, Victoria
dc.contributor.authorRodrigues, João
dc.contributor.authorTomás, Helena
dc.contributor.authorPêgo, Ana P.
dc.date.accessioned2019-06-28T09:16:03Z
dc.date.available2019-06-28T09:16:03Z
dc.date.issued2018
dc.description.abstractDrug delivery to the central nervous system is restricted by the blood-brain barrier (BBB). However, with the onset of stroke, the BBB becomes leaky, providing a window of opportunity to passively target the brain. Here, cationic poly(amido amine) (PAMAM) dendrimers of different generations were functionalized with poly(ethylene glycol) (PEG) to reduce cytotoxicity and prolong blood circulation half-life, aiming for a safe in vivo drug delivery system in a stroke scenario. Rhodamine B isothiocyanate (RITC) was covalently tethered to the dendrimer backbone and used as a small surrogate drug as well as for tracking purposes. The biocompatibility of PAMAM was markedly increased by PEGylation as a function of dendrimer generation and degree of functionalization. The PEGylated RITC-modified dendrimers did not affect the integrity of an in vitro BBB model. Additionally, the functionalized dendrimers remained safe when in contact with the bEnd.3 cells and rat primary astrocytes composing the in vitro BBB model after hypoxia induced by oxygen-glucose deprivation. Modification with PEG also decreased the interaction and uptake by endothelial cells of PAMAM, indicating that the transport across a leaky BBB due to focal brain ischemia would be facilitated. Next, the functionalized dendrimers were tested in contact with red blood cells showing no haemolysis for the PEGylated PAMAM, in contrast to the unmodified dendrimer. Interestingly, the PEG-modified dendrimers reduced blood clotting, which may be an added beneficial function in the context of stroke. The optimized PAMAM formulation was intravenously administered in mice after inducing permanent focal brain ischemia. Twenty-four hours after administration, dendrimers could be detected in the brain, including in neurons of the ischemic cortex. Our results suggest that the proposed formulation has the potential for becoming a successful delivery vector for therapeutic application to the injured brain after stroke reaching the ischemic neurons.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationSantos, S. D., Xavier, M., Leite, D. M., Moreira, D. A., Custódio, B., Torrado, M., ... & Pêgo, A. P. (2018). PAMAM dendrimers: Blood-brain barrier transport and neuronal uptake after focal brain ischemia. Journal of Controlled Release, 291, 65-79.pt_PT
dc.identifier.doi10.1016/j.jconrel.2018.10.006pt_PT
dc.identifier.issn0168-3659
dc.identifier.urihttp://hdl.handle.net/10400.13/2441
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationBaiTS - Biodegradable dendrimers for Targeted neuroprotective therapies in Stroke
dc.relationStrategic Project - UI 674 - 2014
dc.relationModulation of Rac1 towards Neuroprotection in Stroke.
dc.subjectDendrimerspt_PT
dc.subjectDendrimers Poly(amidoamine) PAMAMpt_PT
dc.subjectPoly(ethyleneglycol) PEGpt_PT
dc.subjectNanomaterialspt_PT
dc.subjectNanomedicinept_PT
dc.subjectDrug deliverypt_PT
dc.subjectBlood-brainbarrierpt_PT
dc.subjectBrainischemiapt_PT
dc.subjectStrokept_PT
dc.subjectIn vivopt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.subjectCentro de Química da Madeira
dc.titlePAMAM dendrimers: blood-brain barrier transport and neuronal uptake after focal brain ischemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleBaiTS - Biodegradable dendrimers for Targeted neuroprotective therapies in Stroke
oaire.awardTitleStrategic Project - UI 674 - 2014
oaire.awardTitleModulation of Rac1 towards Neuroprotection in Stroke.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FCTM-NAN%2F112428%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FCTM-NAN%2F3547%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FQUI%2FUI0674%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F109297%2F2015/PT
oaire.citation.endPage79pt_PT
oaire.citation.startPage65pt_PT
oaire.citation.titleJournal of Controlled Releasept_PT
oaire.citation.volume291pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream9471 - RIDTI
oaire.fundingStream6817 - DCRRNI ID
person.familyNameLopes Custódio
person.familyNameFalcão Torrado
person.familyNameCastro
person.familyNameLeiro
person.familyNameRodrigues
person.familyNameTomás
person.familyNamePêgo
person.givenNameBeatriz Maria
person.givenNameMarília Judite
person.givenNameRita
person.givenNameVictoria
person.givenNameJoão
person.givenNameHelena
person.givenNameAna Paula
person.identifier556975
person.identifier164495
person.identifier.ciencia-id0219-F7E0-A69D
person.identifier.ciencia-id1313-C2D0-4125
person.identifier.ciencia-id8314-881E-4986
person.identifier.ciencia-id7713-0BE4-AC65
person.identifier.ciencia-idA81C-620E-DD6A
person.identifier.ciencia-id4D14-D31E-A8BE
person.identifier.ciencia-id6114-92F0-E64C
person.identifier.orcid0000-0003-0817-3216
person.identifier.orcid0000-0003-4798-0002
person.identifier.orcid0000-0002-9337-062X
person.identifier.orcid0000-0002-8907-9151
person.identifier.orcid0000-0003-4552-1953
person.identifier.orcid0000-0002-7856-2041
person.identifier.orcid0000-0001-5169-328X
person.identifier.ridA-2497-2013
person.identifier.ridK-1271-2013
person.identifier.ridB-6816-2008
person.identifier.ridE-5991-2010
person.identifier.ridC-6942-2012
person.identifier.scopus-author-id9634048000
person.identifier.scopus-author-id9233278800
person.identifier.scopus-author-id6508104177
person.identifier.scopus-author-id56053889300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication4d0f36e0-ab95-464b-8de9-20c3e136e32c
relation.isAuthorOfPublication8bb302ce-45f4-42b8-8f50-adafae3ea2eb
relation.isAuthorOfPublicationceb211d0-5522-42ba-bbf0-adfc23f37f84
relation.isAuthorOfPublicationc0f0f395-cfba-470b-8e1b-8d7bfb9e5ab3
relation.isAuthorOfPublication53031fca-b2e7-4ce4-bda9-61e486da4547
relation.isAuthorOfPublication3a747114-6ab9-454b-985b-00cbf792e273
relation.isAuthorOfPublication905a2f89-0018-47d3-850d-4b09bed65b5f
relation.isAuthorOfPublication.latestForDiscoveryceb211d0-5522-42ba-bbf0-adfc23f37f84
relation.isProjectOfPublication2afe1e5d-db36-40da-b776-d8e3015d4fa5
relation.isProjectOfPublicatione411ff7b-e6ea-4f25-9685-531da2acdace
relation.isProjectOfPublication75aaadc4-cd17-4fec-ba9d-1d0e564b3731
relation.isProjectOfPublicationd7176ae0-4138-4b27-adc1-8a04614fddff
relation.isProjectOfPublication.latestForDiscoveryd7176ae0-4138-4b27-adc1-8a04614fddff

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
PAMAM dendrimers blood-brain barrier transport and neuronal uptake after focal brain ischemia.pdf
Size:
3.51 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artigos em revistas internacionais