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Co-delivery of Sildenafil (Viagra®) and Crizotinib for Synergistic and Improved Anti-tumoral Therapy

2014-03-13Journal article Restricted access
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dc.contributor.authorMarques, João Filipe Gonçalves
dc.contributor.authorGaspar, Vítor Manuel Abreu
dc.contributor.authorOppolzer, David
dc.contributor.authorCosta, Elisabete C.
dc.contributor.authorGallardo, Eugenia
dc.contributor.authorCorreia, Ilídio Joaquim Sobreira
dc.date.accessioned2018-03-20T12:00:22Z
dc.date.available2018-03-20T12:00:22Z
dc.date.issued2014-03-13
dc.description.abstractPurpose Cancer multi-drug resistance is a major issue associated with current anti-tumoral therapeutics. In this work, Crizotinib an anti-tumoral drug approved for the treatment of non-small lung cancer in humans, and Sildenafil (Viagra®), were loaded into micellar carriers to evaluate the establishment of a possible synergistic anti-tumoral effect in breast cancer cells. Methods Micellar carriers comprised by PEG-PLA block co-polymers were formulated by the solvent displacement method in which the simultaneous encapsulation of Crizotinib and Sildenafil was promoted. Encapsulation efficiency was analyzed by a new UPLC method validated for this combination of compounds. Micelle physicochemical characterization and cellular uptake were characterized by light scattering and confocal microscopy. The bio- and hemocompatibility of the carriers was also evaluated. MCF-7 breast cancer cells were used to investigate the synergistic anti-tumoral effect. Results Our results demonstrate that this particular combination induces massive apoptosis of breast cancer cells. The co-delivery of Crizotinib and Sildenafil was only possible due to the high encapsulation efficiency of the micellar systems (>70%). The micelles with size ranging between 93 and 127 nm were internalized by breast cancer cells and subsequently released their payload in the intracellular compartment. The results obtained demonstrated that the delivery of both drugs by micellar carriers led to a 2.7 fold increase in the anti-tumoral effect, when using only half of the concentration that is required when free drugs are administered. Conclusions Altogether, co-delivery promoted a synergistic effect and demonstrated for the first time the potential of PEG-PLA-Crizotinib-Sildenafil combination for application in cancer therapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMarques, J.G., Gaspar, V.M., Markl, D., Costa, E.C., Gallardo, E. e Correia, I.J. (2014) "Co-delivery of Sildenafil (Viagra®) and Crizotinib for synergistic and improved anti-tumoral therapy", Pharmaceutical Research, Vol. 31(9), pp. 2516-2528pt_PT
dc.identifier.doi10.1007/s11095-014-1347-xpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/4656
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.relationIsolation and Purification of Plasmid DNA for Cancer Therapy
dc.relationStrategic Project - UI 709 - 2011-2012
dc.relationBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
dc.relation.publisherversionhttps://link.springer.com/article/10.1007%2Fs11095-014-1347-xpt_PT
dc.subjectAnti-tumoral effectpt_PT
dc.subjectBlock co-polymerspt_PT
dc.subjectBreast cancerpt_PT
dc.subjectCo-deliverypt_PT
dc.subjectSynergistic effectpt_PT
dc.titleCo-delivery of Sildenafil (Viagra®) and Crizotinib for Synergistic and Improved Anti-tumoral Therapypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleIsolation and Purification of Plasmid DNA for Cancer Therapy
oaire.awardTitleStrategic Project - UI 709 - 2011-2012
oaire.awardTitleBIOSYNTHESIS AND PURIFICATION OF MINICIRCLE DNA FOR APPLICATION IN DIABETES CELL-SPECIFIC GENE THERAPY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEME-TME%2F103375%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FEBB-BIO%2F114320%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6820 - DCRRNI ID/PEst-C%2FSAU%2FUI0709%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F80402%2F2011/PT
oaire.citation.endPage2528pt_PT
oaire.citation.startPage2516pt_PT
oaire.citation.titlePharmaceutical Researchpt_PT
oaire.citation.volume31pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream6820 - DCRRNI ID
oaire.fundingStreamFARH
person.familyNameGaspar
person.familyNameOppolzer
person.familyNameda Rocha Costa
person.familyNameGallardo
person.familyNameJoaquim Sobreira Correia
person.givenNameVítor
person.givenNameDavid
person.givenNameElisabete Cristina
person.givenNameEugenia
person.givenNameIlídio
person.identifier908303
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person.identifier.ciencia-idB314-4CF0-6633
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person.identifier.ciencia-idF610-7373-DC81
person.identifier.orcid0000-0002-0372-2493
person.identifier.orcid0000-0002-8888-4976
person.identifier.orcid0000-0002-0490-0095
person.identifier.orcid0000-0002-1802-8998
person.identifier.orcid0000-0003-1613-9675
person.identifier.ridB-1602-2017
person.identifier.ridM-7410-2017
person.identifier.scopus-author-id36968590900
person.identifier.scopus-author-id55623902200
person.identifier.scopus-author-id55805850100
person.identifier.scopus-author-id24721485300
person.identifier.scopus-author-id7003557499
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.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
rcaap.embargofctCopyright cedido à editora no momento da publicaçãopt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
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