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Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models

2021-08-21Journal article Open access
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dc.contributor.authorGranja, Andreia
dc.contributor.authorSousa, Rita Lima
dc.contributor.authorAlves, Cátia
dc.contributor.authorDiogo, Duarte de Melo
dc.contributor.authorPinheiro, Marina
dc.contributor.authorSousa, Célia T.
dc.contributor.authorCorreia, I.J.
dc.contributor.authorReis, Salette
dc.date.accessioned2021-08-30T08:24:07Z
dc.date.available2023-08-29T00:30:23Z
dc.date.issued2021-08-21
dc.description.abstractBreast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer.pt_PT
dc.description.versioninfo:eu-repo/semantics/acceptedVersionpt_PT
dc.identifier.doi10.1016/j.ijpharm.2021.121044pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/11204
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationInjectable in situ forming graphene-based hydrogels for double immune checkpoint inhibitor photothermal therapy
dc.relationDevelopment of a responsive multi-layer microneedle patch for the sequential PTT/PDT and immunotherapy of invasive breast cancer
dc.relation.publisherversionhttps://reader.elsevier.com/reader/sd/pii/S0378517321008504?token=F41B30A6670F5E165393DE61CCE6929A7A72A745EBC7F8701D1CE499DB1AE17A61007445072C8E983D55466BC9C93E10&originRegion=eu-west-1&originCreation=20210829144244pt_PT
dc.subjectSolid lipid nanoparticles (SLN)pt_PT
dc.subjectMitoxantronept_PT
dc.subjectBox-Behnken designpt_PT
dc.subjectChemotherapypt_PT
dc.subjectBreast cancerpt_PT
dc.subjectTumor spheroidspt_PT
dc.titleMitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer modelspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleInjectable in situ forming graphene-based hydrogels for double immune checkpoint inhibitor photothermal therapy
oaire.awardTitleDevelopment of a responsive multi-layer microneedle patch for the sequential PTT/PDT and immunotherapy of invasive breast cancer
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F144922%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F145386%2F2019/PT
oaire.citation.conferencePlaceNetherlandspt_PT
oaire.citation.startPage121044pt_PT
oaire.citation.titleInternational Journal of Pharmaceuticspt_PT
oaire.fundingStreamPOR_CENTRO
oaire.fundingStreamPOR_CENTRO
person.familyNameAlmeida Granja
person.familyNameSousa
person.familyNameAlves
person.familyNameMiguel de Melo Diogo
person.familyNameBarroso Pereira Pinheiro
person.familyNamePeixoto de Sousa
person.familyNameJoaquim Sobreira Correia
person.familyNameReis
person.givenNameAndreia
person.givenNameAna Rita Lima
person.givenNameCátia Gomes
person.givenNameDuarte
person.givenNameMarina
person.givenNameCélia Maria
person.givenNameIlídio
person.givenNameSalette
person.identifierC2z5x04AAAAJ
person.identifierUMbJ1KMAAAAJ
person.identifierA-9613-2013
person.identifier.ciencia-id4714-87BC-F3D7
person.identifier.ciencia-idBD19-68AA-7099
person.identifier.ciencia-id8317-7EF2-24C8
person.identifier.ciencia-id9C10-9BD8-634E
person.identifier.ciencia-idED16-98DD-AFA6
person.identifier.ciencia-id3A1F-D90C-B625
person.identifier.ciencia-idF610-7373-DC81
person.identifier.ciencia-id8711-9CCC-B3BA
person.identifier.orcid0000-0001-6437-8190
person.identifier.orcid0000-0003-4764-1967
person.identifier.orcid0000-0001-7066-3051
person.identifier.orcid0000-0001-9984-3603
person.identifier.orcid0000-0002-6931-1355
person.identifier.orcid0000-0001-6876-9906
person.identifier.orcid0000-0003-1613-9675
person.identifier.orcid0000-0002-0736-2835
person.identifier.ridB-1125-2019
person.identifier.scopus-author-id57201215315
person.identifier.scopus-author-id57201213407
person.identifier.scopus-author-id56266511300
person.identifier.scopus-author-id7003557499
person.identifier.scopus-author-id7102060107
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
rcaap.embargofctO copyright foi cedido à revistapt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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