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Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain

dc.contributor.authorTeixeira, Maria Inês
dc.contributor.authorLopes, Carla Martins
dc.contributor.authorGonçalves, Hugo
dc.contributor.authorCatita, José
dc.contributor.authorSilva, Ana Margarida
dc.contributor.authorRodrigues, Francisca
dc.contributor.authorAmaral, Maria Helena
dc.contributor.authorCosta, Paulo C.
dc.date.accessioned2023-01-31T09:17:35Z
dc.date.available2023-01-31T09:17:35Z
dc.date.issued2022-01-13
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brainpt_PT
dc.description.sponsorshipThis work was financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the projects UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO. Maria Inês Teixeira is thankful for the Ph.D. grant (2020.05060.BD) from the Fundação para a Ciência e a Tecnologia (FCT) and for project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB supported through national funds. Ana Margarida Silva is thankful for the Ph.D. grant (SFRH/BD/144994/2019) financed by POPH–QREN and subsidized by the European Science Foundation and Ministério da Ciência, Tecnologia e Ensino Superior. Francisca Rodrigues (CEECIND/01886/2020) is thankful for her contract financed by FCT/MCTES—CEEC Individual Program Contract and for projects UIDB/50006/2020 and UIDP/50006/2020 by the FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) supported through national funds. The authors are also grateful to Rui Fernandes and Ana Rita Malheiro (HEMS core facility, i3S, University of Porto) for their assistance with TEM.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/pharmaceutics14010185pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/22016
dc.language.isoengpt_PT
dc.publisherMDPIpt_PT
dc.relationLA/P/0140/2020pt_PT
dc.relationApplied Molecular Biosciences Unit
dc.relationApplied Molecular Biosciences Unit
dc.relationFunctionalized lipid nanocarriers for enhancement of blood-brain barrier BBB permeability in the treatment of amyotrophic lateral sclerosis
dc.relationFrom soil to skin: Eco-friendly extract from kiwiberry leaves for prevention of skin aging process
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relation.publisherversionhttps://www.mdpi.com/1999-4923/14/1/185pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectBlood–brain barrier (BBB)pt_PT
dc.subjectBrain deliverypt_PT
dc.subjectNeurodegenerative diseasespt_PT
dc.subjectAmyotrophic lateral sclerosis (ALS)pt_PT
dc.subjectLipid nanoparticlespt_PT
dc.subjectNanostructured lipid carriers (NLC)pt_PT
dc.subjectRiluzolept_PT
dc.subjectLactoferrinpt_PT
dc.subjectLactoferrin receptorspt_PT
dc.subjectDrug targetingpt_PT
dc.titleFormulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brainpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleApplied Molecular Biosciences Unit
oaire.awardTitleFunctionalized lipid nanocarriers for enhancement of blood-brain barrier BBB permeability in the treatment of amyotrophic lateral sclerosis
oaire.awardTitleFrom soil to skin: Eco-friendly extract from kiwiberry leaves for prevention of skin aging process
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//2020.05060.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F144994%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F50006%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT
oaire.citation.issue1pt_PT
oaire.citation.startPage185pt_PT
oaire.citation.titlePharmaceuticspt_PT
oaire.citation.volume14pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamPOR_NORTE
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameSilva
person.familyNamePinto Lisboa Martins Rodrigues Sarmento
person.givenNameAna Margarida
person.givenNameFrancisca
person.identifier1552042
person.identifier.ciencia-id5C16-8C22-EF1E
person.identifier.ciencia-id4F19-3D98-2CBA
person.identifier.orcid0000-0002-1823-9816
person.identifier.orcid0000-0001-8803-0041
person.identifier.scopus-author-id57203495060
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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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
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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