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Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

2018-06Journal article Open access
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dc.contributor.authorCunha, Ludmylla Costa
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.accessioned2018-12-07T14:53:25Z
dc.date.available2018-12-07T14:53:25Z
dc.date.issued2018-06
dc.description.abstractThe pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.
dc.description.sponsorshipPortuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4]
dc.identifier.doi10.3390/polym10060636
dc.identifier.issn2073-4360
dc.identifier.urihttp://hdl.handle.net/10400.1/11510
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.subjectDry Powder Inhalers
dc.subjectAlveolar Macrophages
dc.subjectAerodynamic Performance
dc.subjectIn-Vitro
dc.subjectDelivery
dc.subjectRifabutin
dc.subjectRifampicin
dc.subjectPolysaccharides
dc.subjectNanoparticles
dc.subjectMicrospheres
dc.titleInhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F0094%2F2012/PT
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.issue6
oaire.citation.startPage636
oaire.citation.titlePolymers
oaire.citation.volume10
oaire.fundingStream3599-PPCDT
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.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.rightsopenAccess
rcaap.typearticle
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