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Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection

2020-02Journal article Restricted access
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dc.contributor.authorGrenha, Ana
dc.contributor.authorAlves, Ana D.
dc.contributor.authorGuerreiro, Filipa
dc.contributor.authorPinho, Jacinta
dc.contributor.authorSimões, Sandra
dc.contributor.authorAlmeida, António José
dc.contributor.authorGaspar, Maria Manuela
dc.date.accessioned2020-04-02T13:12:34Z
dc.date.available2021-02-01T01:30:14Z
dc.date.issued2020-02
dc.description.abstractTuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96.pt_PT
dc.description.sponsorshipUID/DTP/04138/2019; UID/Multi/04326/2019; FRH/BD/115628/2016pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.ejpb.2019.11.009pt_PT
dc.identifier.issn0939-6411
dc.identifier.urihttp://hdl.handle.net/10400.1/13683
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.relationKonjac glucomannan microcarriers: an application in the treatment of pulmonary tuberculosis
dc.subjectTuberculosispt_PT
dc.subjectPulmonary deliverypt_PT
dc.subjectLocust bean gumpt_PT
dc.subjectSpray-dried microparticlespt_PT
dc.subjectRifabutin; isoniazidpt_PT
dc.subjectIn vivo studiespt_PT
dc.titleInhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
oaire.awardTitleKonjac glucomannan microcarriers: an application in the treatment of pulmonary tuberculosis
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//SFRH%2FBD%2F115628%2F2016/PT
oaire.citation.endPage44pt_PT
oaire.citation.startPage38pt_PT
oaire.citation.titleEuropean Journal of Pharmaceutics and Biopharmaceuticspt_PT
oaire.citation.volume147pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
person.familyNameGrenha
person.familyNameGuerreiro
person.givenNameAna
person.givenNameFilipa
person.identifier.ciencia-id091C-0D58-7225
person.identifier.ciencia-idBF1D-7EFA-19BC
person.identifier.orcid0000-0002-2136-1396
person.identifier.orcid0000-0001-6224-1553
person.identifier.ridH-1392-2017
person.identifier.scopus-author-id8607930100
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.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublicationb88abfe8-e32c-477f-9fb0-5bdeca8a1a05
relation.isAuthorOfPublication.latestForDiscovery1bd4d8f1-40e5-45af-b1e8-4b8e73a6a70d
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