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Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

dc.contributor.authorRodrigues, Susana
dc.contributor.authorAlves, Ana D.
dc.contributor.authorCavaco, Joana S.
dc.contributor.authorPontes, Jorge Filipe
dc.contributor.authorGuerreiro, Filipa
dc.contributor.authorRosa Da Costa, Ana
dc.contributor.authorButtini, Francesca
dc.contributor.authorGrenha, Ana
dc.date.accessioned2019-11-20T15:07:25Z
dc.date.available2019-11-20T15:07:25Z
dc.date.issued2017-08
dc.description.abstractDespite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.
dc.description.sponsorshipNational Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011]
dc.identifier.doi10.1016/j.ijpharm.2017.06.088
dc.identifier.issn0378-5173
dc.identifier.issn1873-3476
dc.identifier.urihttp://hdl.handle.net/10400.1/13031
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationDEVELOPMENT OF POLYSACCHARIDE-BASED CARRIERS FOR PULMONARY TUBERCULOSIS THERAPY
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.subjectAlveolar macrophages
dc.subjectPhysicochemical properties
dc.subjectIn-vitro
dc.subjectNanoparticles
dc.subjectPowder
dc.subjectFormulations
dc.subjectChitosan
dc.subjectDesign
dc.subjectInhalation
dc.subjectDeposition
dc.titleDual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDEVELOPMENT OF POLYSACCHARIDE-BASED CARRIERS FOR PULMONARY TUBERCULOSIS THERAPY
oaire.awardTitleFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F52426%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F0094%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FQUI%2F00100%2F2013/PT
oaire.citation.endPage441
oaire.citation.issue01-fev
oaire.citation.startPage433
oaire.citation.titleInternational Journal of Pharmaceutics
oaire.citation.volume529
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameRodrigues
person.familyNamePontes
person.familyNameGuerreiro
person.familyNameRosa da Costa
person.familyNameGrenha
person.givenNameSusana
person.givenNameJorge Filipe
person.givenNameFilipa
person.givenNameAna M
person.givenNameAna
person.identifier305029
person.identifier.ciencia-id9D1A-6537-0383
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person.identifier.ciencia-id091C-0D58-7225
person.identifier.orcid0000-0002-0329-4265
person.identifier.orcid0000-0002-6447-0242
person.identifier.orcid0000-0001-6224-1553
person.identifier.orcid0000-0003-0225-9537
person.identifier.orcid0000-0002-2136-1396
person.identifier.ridE-2165-2012
person.identifier.ridH-1392-2017
person.identifier.scopus-author-id55125292100
person.identifier.scopus-author-id57195033461
person.identifier.scopus-author-id53986075100
person.identifier.scopus-author-id8607930100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
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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
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
rcaap.typearticle
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