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Understanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatment

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dc.contributor.authorMartin, Victor
dc.contributor.authorRibeiro, Isabel A. C.
dc.contributor.authorAlves, Marta M.
dc.contributor.authorGonçalves, Lídia
dc.contributor.authorAlmeida, António José
dc.contributor.authorGrenho, Liliana
dc.contributor.authorFernandes, Maria H.
dc.contributor.authorSantos, Catarina F.
dc.contributor.authorGomes, Pedro S.
dc.contributor.authorBettencourt, Ana
dc.date.accessioned2024-01-22T17:20:07Z
dc.date.available2024-01-22T17:20:07Z
dc.date.issued2019
dc.date.updated2023-02-27T16:39:45Z
dc.description© 2019 Elsevier B.V. All rights reserved.pt_PT
dc.description.abstractPeriodontal diseases remain a challenge due to a complex interplay of factors involving a chronic inflammatory activation and bacteria internalization in periodontal cells. In this work, chitosan-nanoparticles loaded with minocycline (MH-NPs), a tetracycline with antimicrobial and anti-inflammatory effects, were developed for in situ delivery in the periodontal milieu aiming to improve drug effectiveness. A general cytocompatibility evaluation and a detailed approach to address the cellular uptake process, trafficking pathways and the modulation of relevant inflammatory gene expression was conducted using human gingival fibroblasts. Results show that MH-NPs with an adequate cytocompatible profile can be internalized by distinct endocytic processes (macropinocytosis and clathrin-mediated endocytosis). The ability to modulate autophagy with the delivery within the same endosomal/lysosomal pathway as periodontal pathogens was observed, which increases the intracellular drug effectiveness. Porphyromonas gingivalis LPS-stimulated cultures, grown in the presence of MH-NPs, were found to express significantly reduced levels of inflammation-related markers (IL-1b, TNFα, CXCL-8, NFKB1). These nanoparticles can be potentially used in periodontal disease treatment conjoining the ability of intracellular drug targeting with significant anti-inflammatory effects.pt_PT
dc.description.sponsorshipThe authors would like to thank the Portuguese government, Fundação para a Ciência e Tecnologia (FCT), for the financial support through national funds under iMED.ULisboa project Pest-UID/DTP/04138/2019, CQE project UID/QUI/00100/2019 and UID/QUI/50006/2019.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMartin V, Ribeiro IAC, Alves MM, Gonçalves L, Almeida AJ, Grenho L, et al. Understanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatment. International Journal of Pharmaceutics [Internet]. dezembro de 2019;572:118821. Disponível em: https://linkinghub.elsevier.com/retrieve/pii/S037851731930866Xpt_PT
dc.identifier.doi10.1016/j.ijpharm.2019.118821pt_PT
dc.identifier.eid2-s2.0-85075787156
dc.identifier.slugcv-prod-2420945
dc.identifier.urihttp://hdl.handle.net/10451/62014
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationResearch Institute for Medicines
dc.relationCentro de Química Estrutural
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S037851731930866Xpt_PT
dc.subjectChitosanpt_PT
dc.subjectMinocyclinept_PT
dc.subjectIntracellular-target deliverypt_PT
dc.subjectPerioceuticspt_PT
dc.subjectInflammationpt_PT
dc.subjectPeriodontitispt_PT
dc.titleUnderstanding intracellular trafficking and anti-inflammatory effects of minocycline chitosan-nanoparticles in human gingival fibroblasts for periodontal disease treatmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleResearch Institute for Medicines
oaire.awardTitleCentro de Química Estrutural
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FDTP%2F04138%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00100%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F50006%2F2019/PT
oaire.citation.startPage118821pt_PT
oaire.citation.titleInternational Journal of Pharmaceuticspt_PT
oaire.citation.volume572pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameMartin
person.familyNameRibeiro
person.familyNameDiogo Gonçalves
person.familyNameLeitão das Neves Almeida
person.familyNameCampos Simão Bettencourt
person.givenNameVictor
person.givenNameIsabel
person.givenNameLídia Maria
person.givenNameAntónio José
person.givenNameAna Francisca
person.identifier1165976
person.identifier163977
person.identifierI-6590-2012
person.identifierM-4219-2013
person.identifier.ciencia-id8E11-3702-A008
person.identifier.ciencia-idE31A-26B8-4AC6
person.identifier.ciencia-id7211-22BA-86AD
person.identifier.ciencia-id8312-F853-C47A
person.identifier.ciencia-id7C1F-F932-33DC
person.identifier.orcid0000-0001-6910-1705
person.identifier.orcid0000-0002-7110-6393
person.identifier.orcid0000-0002-6799-2740
person.identifier.orcid0000-0002-7807-4726
person.identifier.orcid0000-0002-8498-5892
person.identifier.ridA-6098-2014
person.identifier.scopus-author-id57195675698
person.identifier.scopus-author-id22836446000
person.identifier.scopus-author-id57195052432
person.identifier.scopus-author-id6603687672
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
rcaap.cv.cienciaid7211-22BA-86AD | Lídia Maria Diogo Gonçalves
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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