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Carrageenan from red algae: an application in the development of inhalable tuberculosis therapy targeting the macrophages

dc.contributor.authorRodrigues, Susana
dc.contributor.authorCunha, Ludmylla Costa
dc.contributor.authorMartins Rico, João
dc.contributor.authorRosa Da Costa, Ana
dc.contributor.authorAlmeida, Antonio J.
dc.contributor.authorFaleiro, ML
dc.contributor.authorButtini, Francesca
dc.contributor.authorGrenha, Ana
dc.date.accessioned2021-06-24T11:35:29Z
dc.date.available2021-06-24T11:35:29Z
dc.date.issued2020-12
dc.description.abstractMacrophages have unique surface receptors that might recognize preferentially several moieties present on the surface of infecting organisms, including in the bacterial cell wall. Benefiting from a similar composition regarding the referred moieties, polysaccharides might be good candidates to compose the matrix of drug carriers aimed at macrophage targeting, as they can use the same recognition pathways of the infecting organisms. Carrageenan (CRG), a polysaccharide extracted from red edible seaweed, is an interesting possibility for the approach of directly targeting alveolar macrophages, as its composition is reported to be recognized by several macrophage lectin receptors. Inhalable starch/CRG microparticles were successfully produced, effectively associating isoniazid (96%) and rifabutin (74%) 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 3.3 and 3.9 mu m. It was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells for the drug-loaded formulation. Starch/CRG 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. This work provides indications on the potential of the starch/CRG carriers to interact with macrophages, thus providing a platform for drug delivery in the context of macrophage intracellular diseases. Additionally, if tuberculosis is focused, these microparticles can be used as inhalable drug carriers.
dc.description.sponsorshipPortuguese Foundation for Science and Technology (FCT)Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2019, UID/BIM/04773/2013, SFRH/BD/52426/2013]
dc.description.versioninfo:eu-repo/semantics/acceptedVersion
dc.identifier.doi10.1007/s13346-020-00799-0
dc.identifier.issn2190-393X
dc.identifier.urihttp://hdl.handle.net/10400.1/16454
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.subjectAlveolar macrophages
dc.subjectCarrageenan
dc.subjectLung deposition
dc.subjectMacrophage activation
dc.subject.otherInstruments & instrumentation
dc.titleCarrageenan from red algae: an application in the development of inhalable tuberculosis therapy targeting the macrophages
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%2FBIM%2F04773%2F2013/PT
oaire.citation.endPage1687
oaire.citation.issue6
oaire.citation.startPage1675
oaire.citation.titleDrug Delivery and Translational Research
oaire.citation.volume10
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
person.familyNameRodrigues
person.familyNameCunha
person.familyNameMartins Rico
person.familyNameRosa da Costa
person.familyNameFaleiro
person.familyNameGrenha
person.givenNameSusana
person.givenNameLudmylla Costa
person.givenNameJoão
person.givenNameAna M
person.givenNameMaria Leonor
person.givenNameAna
person.identifier305029
person.identifier252666
person.identifier.ciencia-id9D1A-6537-0383
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person.identifier.ciencia-id281D-5E01-F09A
person.identifier.ciencia-id091C-0D58-7225
person.identifier.orcid0000-0002-0329-4265
person.identifier.orcid0000-0003-2620-5760
person.identifier.orcid0000-0002-9701-3750
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.rightsrestrictedAccess
rcaap.typearticle
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