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Enfuvirtide-protoporphyrin IX dual-loaded liposomes: in vitro evidence of synergy against HIV-1 entry into cells

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dc.contributor.authorFigueira, Tiago Nascimento
dc.contributor.authorDomingues, Marco
dc.contributor.authorIllien, Françoise
dc.contributor.authorCadima Couto, Carla Iris
dc.contributor.authorTodorovski, Toni
dc.contributor.authorAndreu, David
dc.contributor.authorSagan, Sandrine
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorWalrant, Astrid
dc.contributor.authorVeiga, Ana Salomé
dc.date.accessioned2023-05-05T15:42:30Z
dc.date.available2023-05-05T15:42:30Z
dc.date.issued2020
dc.description© 2019 American Chemical Societypt_PT
dc.description.abstractWe have developed a nanocarrier consisting of large unilamellar vesicles (LUVs) for combined delivery of two human immunodeficiency virus type 1 (HIV-1) entry inhibitors, enfuvirtide (ENF) and protoporphyrin IX (PPIX). The intrinsic lipophilicity of ENF and PPIX, a fusion inhibitor and an attachment inhibitor, respectively, leads to their spontaneous incorporation into the lipid bilayer of the LUVs nanocarrier. Both entry inhibitors partition significantly toward LUVs composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and a 9:1 mixture of POPC:1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (DPPE-PEG2000), representative of conventional and immune-evasive drug delivery formulations, respectively. These colocalize in the core of lipid membranes. Dual-loaded nanocarriers are monodispersed and retain the size distribution, thermotropic behavior, and surface charge of the unloaded form. Combination of the two entry inhibitors in the nanocarrier resulted in improved synergy against HIV-1 entry compared to combination in free form, strongly when immuneevasive formulations are used. We propose that the improved action of the entry inhibitors when loaded into the nanocarriers results from their slow release at the site of viral entry. Overall, liposomes remain largely unexplored platforms for combination of viral entry inhibitors, with potential for improvement of current antiretroviral therapy drug safety and application. Our work calls for a reappraisal of the potential of entry inhibitor combinations and delivery for clinical use in antiretroviral therapy.pt_PT
dc.description.sponsorshipThis work was supported by European Research Area Networks (ERA-Net) project HIVERA/0002/2013 and Fundação para a Ciência e a Tecnologia (FCT-MCTES) project VIH/SAU/0029/2011. This work has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 828774. T.N.F., M.M.D., and I.C. acknowledge individual fellowships SFRH/BD/5283/2013, SFRH/BPD/122779/2016, and SFRH/BPD/65531/2009 funded by FCT-MCTES, respectively. A.S.V. acknowledges funding under the Investigator Programme (IF/00803/2012) from FCT-MCTES.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationACS Infect. Dis. 2020, 6, 224−236pt_PT
dc.identifier.doi10.1021/acsinfecdis.9b00285pt_PT
dc.identifier.eissn2373-8227
dc.identifier.urihttp://hdl.handle.net/10451/57373
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherACS Publicationspt_PT
dc.relationSFRH/BD/5283/2013pt_PT
dc.relation''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
dc.relationDelivery and targeting fibrinolytic agents to blood clots
dc.relationMULTI-TARGET HIV ENTRY INHIBITORS DELIVERY BY CATIONIC LIPOSOMES
dc.relationTowards the development of antimicrobial peptides with antibacterial activity against resistant bacteria and bacterial biofilms
dc.relation.publisherversionhttps://pubs.acs.org/journal/aidcbcpt_PT
dc.subjectHIVpt_PT
dc.subjectEntrypt_PT
dc.subjectInhibitorpt_PT
dc.subjectLiposomept_PT
dc.subjectMembranept_PT
dc.subjectNanocarrierpt_PT
dc.subjectDeliverypt_PT
dc.titleEnfuvirtide-protoporphyrin IX dual-loaded liposomes: in vitro evidence of synergy against HIV-1 entry into cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitle''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
oaire.awardTitleDelivery and targeting fibrinolytic agents to blood clots
oaire.awardTitleMULTI-TARGET HIV ENTRY INHIBITORS DELIVERY BY CATIONIC LIPOSOMES
oaire.awardTitleTowards the development of antimicrobial peptides with antibacterial activity against resistant bacteria and bacterial biofilms
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HIVERA%2F0002%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/VIH%2FSAU%2F0029%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/828774/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBPD%2F122779%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBPD%2F65531%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Investigador FCT/IF%2F00803%2F2012%2FCP0191%2FCT0001/PT
oaire.citation.endPage236pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage224pt_PT
oaire.citation.titleACS Infectious Diseasespt_PT
oaire.citation.volume6pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
oaire.fundingStreamOE
oaire.fundingStreamFARH
oaire.fundingStreamInvestigador FCT
person.familyNameFigueira
person.familyNameDomingues
person.familyNamecadima couto
person.familyNameCastanho
person.familyNameVeiga
person.givenNameTiago
person.givenNameMarco
person.givenNamecarla iris
person.givenNameMiguel
person.givenNameAna Salome
person.identifier.ciencia-idE317-92F8-84C6
person.identifier.orcid0000-0002-0813-0745
person.identifier.orcid0000-0003-1502-1421
person.identifier.orcid0000-0001-7398-5857
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-9892-2243
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id56745037100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
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.nameEuropean Commission
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.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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