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Gas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugs

2015-07-09Journal article Restricted access
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dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorMoreira, André
dc.contributor.authorCosta, Elisabete C.
dc.contributor.authorQueiroz, João
dc.contributor.authorSousa, Fani
dc.contributor.authorPichon, Chantal
dc.contributor.authorCorreia, Ilídio Joaquim Sobreira
dc.date.accessioned2018-03-21T09:23:25Z
dc.date.available2018-03-21T09:23:25Z
dc.date.issued2015-07-09
dc.description.abstractDrug-DNA combination therapies are receiving an ever growing focus due to their potential for improving cancer treatment. However, such approaches are still limited by the lack of multipurpose delivery systems that encapsulate drugs and condense DNA simultaneously. In this study, we describe the successful formulation of gas-generating pH-responsive D-α-tocopherol PEG succinate-poly(d,l-lactic-co-glycolic acid) (TPGS-PLGA) hollow microspheres loaded with both Doxorubicin (Dox) and minicircle DNA (mcDNA) nanoparticles as a strategy to co-deliver these therapeutics. For this study mcDNA vectors were chosen due to their increased therapeutic efficiency in comparison to standard plasmid DNA. The results demonstrate that TPGS-PLGA microcarriers can encapsulate Dox and chitosan nanoparticles completely condense mcDNA. The loading of mcDNA-nanoparticles into microspheres was confirmed by 3D confocal microscopy and co-localization analysis. The resulting TPGS-PLGA-Dox-mcDNA nanoparticle-in-microsphere hybrid carriers exhibit a well-defined spherical shape and neutral surface charge. Microcarriers incubation in acidic pH produced a gas-mediated Dox release, corroborating the microcarriers stimuli-responsive character. Also, the dual-loaded TPGS-PLGA particles achieved 5.2-fold higher cellular internalization in comparison with non-pegylated microspheres. This increased intracellular concentration resulted in a higher cytotoxic effect. Successful transgene expression was obtained after nanoparticle-mcDNA co-delivery in the microspheres. Overall these findings support the concept of using nanoparticle-microsphere multipart systems to achieve efficient co-delivery of various drug-mcDNA combinations.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGaspar, V.M., Moreira, A.F., Costa, E.C., Queiroz, J.A., Sousa, F., Pichon, C. e Correia, I.J. (2015) “Gas-generating TPGS-PLGA Microspheres loaded with Nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugs”, Colloids and Surfaces B: Biointerfaces, Vol. 134, pp.287-294pt_PT
dc.identifier.doi10.1016/j.colsurfb.2015.07.004pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4674
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationStrategic Project - UI 709 - 2011-2012
dc.relation2014 - Strategic Project
dc.relationBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S0927776515300382?via%3Dihubpt_PT
dc.subjectMicrospherespt_PT
dc.subjectCo-deliverypt_PT
dc.subjectMinicircle DNApt_PT
dc.subjectDrugspt_PT
dc.subjectNanoparticlespt_PT
dc.titleGas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleStrategic Project - UI 709 - 2011-2012
oaire.awardTitle2014 - Strategic Project
oaire.awardTitleBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FSAU%2FUI0709%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FSAU%2FUI0709%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F80402%2F2011/PT
oaire.citation.endPage294pt_PT
oaire.citation.startPage287pt_PT
oaire.citation.titleColloids and Surfaces B: Biointerfacespt_PT
oaire.citation.volume134pt_PT
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameGaspar
person.familyNameMoreira
person.familyNameda Rocha Costa
person.familyNameQueiroz
person.familyNameSousa
person.familyNameJoaquim Sobreira Correia
person.givenNameVítor
person.givenNameAndré Ferreira
person.givenNameElisabete Cristina
person.givenNameJoão
person.givenNameFani
person.givenNameIlídio
person.identifier1161643
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person.identifier.ciencia-id991D-2E13-A840
person.identifier.ciencia-idF610-7373-DC81
person.identifier.orcid0000-0002-0372-2493
person.identifier.orcid0000-0002-0604-2506
person.identifier.orcid0000-0002-0490-0095
person.identifier.orcid0000-0002-3096-8325
person.identifier.orcid0000-0001-9996-2194
person.identifier.orcid0000-0003-1613-9675
person.identifier.ridB-1602-2017
person.identifier.ridL-3104-2014
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person.identifier.scopus-author-id36968590900
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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.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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