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Combinatorial delivery of Crizotinib–Palbociclib–Sildenafil using TPGS-PLA micelles for improved cancer treatment

2014-10-13Journal article Restricted access
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dc.contributor.authorDiogo, Duarte Miguel de Melo
dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorCosta, Elisabete C.
dc.contributor.authorMoreira, André
dc.contributor.authorOppolzer, David
dc.contributor.authorGallardo, Eugenia
dc.contributor.authorCorreia, Ilídio Joaquim Sobreira
dc.date.accessioned2018-03-20T14:32:56Z
dc.date.available2018-03-20T14:32:56Z
dc.date.issued2014-10-13
dc.description.abstractThe co-delivery of multiple chemotherapeutics by micellar delivery systems is a valuable approach to improve cancer treatment since various disease hallmarks can be targeted simultaneously. However, the delivery of multiple drugs requires a nanocarrier structure that can encapsulate various bioactive molecules. In this study, we evaluate the simultaneous encapsulation of a novel triple drug combination in D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactic acid) (TPGS-PLA) amphiphilic micelles for cancer therapy. The drug mixture involves two anti-tumoral drugs, Crizotinib and Palbociclib combined with Sildenafil, a compound that is capable of increasing drug accumulation in the intracellular compartment. Such combination aims to achieve an enhanced cytotoxic effect in cancer cells. Our results demonstrated that TPGS-PLA copolymers self-assembled into stable nanosized micelles (158.3 nm) capable of co-encapsulating the three drugs with high loading efficiency. Triple drug loaded TPGS-PLA micelles were internalized in A549 non-small lung cancer cells and exhibited an improved cytotoxic effect in comparison with single (Crizotinib) or dual (Crizotinib–Palbociclib) drug loaded micelles, indicating the therapeutic potential of the triple co-delivery strategy. These findings demonstrate that TPGS-PLA micelles are suitable carriers for multiple drug delivery and also that this particular drug combination may have potential to improve cancer treatment.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDe Melo-Diogo, D., Gaspar, V.M., Costa, E.C., Moreira, A.F., Markl, D., Gallardo, E. e Correia, I.J. (2014) “Combinatorial delivery of Crizotinib-Palbociclib-Sildenafil using TPGS-PLA micelles for improved cancer treatment”, European Journal of Pharmaceutics and Biopharmaceutics, Vol. 88 (3), pp. 718-729pt_PT
dc.identifier.doi10.1016/j.ejpb.2014.09.013pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4657
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/S0939641114002847pt_PT
dc.subjectCancerpt_PT
dc.subjectCo-deliverypt_PT
dc.subjectMicellar carrierspt_PT
dc.subjectMultidrug therapypt_PT
dc.subjectNon-small cell lung cancerpt_PT
dc.subjectTPGS-PLA copolymerpt_PT
dc.titleCombinatorial delivery of Crizotinib–Palbociclib–Sildenafil using TPGS-PLA micelles for improved cancer treatmentpt_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.endPage729pt_PT
oaire.citation.startPage718pt_PT
oaire.citation.titleEuropean Journal of Pharmaceutics and Biopharmaceuticspt_PT
oaire.citation.volume88pt_PT
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameMiguel de Melo Diogo
person.familyNameGaspar
person.familyNameda Rocha Costa
person.familyNameMoreira
person.familyNameOppolzer
person.familyNameGallardo
person.familyNameJoaquim Sobreira Correia
person.givenNameDuarte
person.givenNameVítor
person.givenNameElisabete Cristina
person.givenNameAndré Ferreira
person.givenNameDavid
person.givenNameEugenia
person.givenNameIlídio
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person.identifier.orcid0000-0001-9984-3603
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person.identifier.orcid0000-0002-1802-8998
person.identifier.orcid0000-0003-1613-9675
person.identifier.ridB-1602-2017
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person.identifier.scopus-author-id56266511300
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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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