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Inhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatment

2019Journal article Open Access
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dc.contributor.authorCunha, Ludmylla
dc.contributor.authorRodrigues, Susana
dc.contributor.authorRosa Da Costa, Ana
dc.contributor.authorFaleiro, Maria Leonor
dc.contributor.authorButtini, Francesca
dc.contributor.authorGrenha, Ana
dc.date.accessioned2020-04-02T10:10:52Z
dc.date.available2020-08-01T00:30:11Z
dc.date.issued2019
dc.description.abstractThe direct delivery of antibiotics to the lung has been considered an effective approach to treat pulmonary tuberculosis, which represents approximately 80% of total cases. In this sense, this work aimed at producing inhalable chitosan microparticles simultaneously associating isoniazid and rifabutin, for an application in pulmonary tuberculosis therapy. Spray-dried chitosan microparticles were obtained with adequate flow properties for deep lung delivery (aerodynamic diameter of 4 µm) and high drug association efficiencies (93% for isoniazid and 99% for rifabutin). The highest concentration of microparticles that was tested (1 mg/mL) decreased the viability of macrophage-differentiated THP-1 cells to around 60% after 24 h exposure, although no deleterious effect was observed in human alveolar epithelial (A549) cells. The release of LDH was, however, increased in both cells. Chitosan microparticles further evidenced capacity to activate macrophage-like cells, inducing cytokine secretion well above basal levels. Moreover, the propensity of macrophages to internalize microparticles was demonstrated, with uptake levels over 90%. Chitosan microparticles also inhibited bacterial growth by 96%, demonstrating that the microencapsulation preserved drug antibacterial activity in vitro. Overall, the obtained data suggest the potential of chitosan microparticles for inhalable lung tuberculosis therapy.pt_PT
dc.description.sponsorshipPTDC/DTP-486 FTO/0094/2012pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1080/03639045.2019.1608231pt_PT
dc.identifier.issn0363-9045
dc.identifier.urihttp://hdl.handle.net/10400.1/13681
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor & Francispt_PT
dc.subjectA549 cellspt_PT
dc.subjectAdministrationpt_PT
dc.subjectAntitubercular agentspt_PT
dc.subjectCell Linept_PT
dc.subjectChitosanpt_PT
dc.subjectDrug carrierspt_PT
dc.subjectHumanspt_PT
dc.subjectIsoniazidpt_PT
dc.subjectLungpt_PT
dc.subjectMacrophagespt_PT
dc.subjectNanoparticlespt_PT
dc.subjectParticle sizept_PT
dc.subjectRifabutinpt_PT
dc.subjectTuberculosispt_PT
dc.subjectTumorpt_PT
dc.subjectAlveolarpt_PT
dc.subjectInhalationpt_PT
dc.subjectPulmonarypt_PT
dc.titleInhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT
oaire.citation.endPage1320pt_PT
oaire.citation.issue8pt_PT
oaire.citation.startPage1313pt_PT
oaire.citation.titleDrug Development and Industrial Pharmacypt_PT
oaire.citation.volume45pt_PT
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameCunha
person.familyNameRodrigues
person.familyNameRosa da Costa
person.familyNameFaleiro
person.familyNameGrenha
person.givenNameLudmylla Costa
person.givenNameSusana
person.givenNameAna M
person.givenNameMaria Leonor
person.givenNameAna
person.identifier305029
person.identifier252666
person.identifier.ciencia-id9D1A-6537-0383
person.identifier.ciencia-idA418-A85E-5DB1
person.identifier.ciencia-id281D-5E01-F09A
person.identifier.ciencia-id091C-0D58-7225
person.identifier.orcid0000-0003-2620-5760
person.identifier.orcid0000-0002-0329-4265
person.identifier.orcid0000-0003-0225-9537
person.identifier.orcid0000-0002-3878-6948
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-id53986075100
person.identifier.scopus-author-id6507927018
person.identifier.scopus-author-id8607930100
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
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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