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Cytocompatibility and cellular interactions of chondroitin sulfate microparticles designed for inhaled tuberculosis treatment

2021-06Journal article Restricted access
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dc.contributor.authorRodrigues, Susana
dc.contributor.authorCunha, Ludmylla Costa
dc.contributor.authorKollan, Julia
dc.contributor.authorNeumann, Paul Robert
dc.contributor.authorCosta, Ana Rosa da
dc.contributor.authorDailey, Lea Ann
dc.contributor.authorGrenha, Ana
dc.date.accessioned2021-09-08T10:57:51Z
dc.date.available2021-09-08T10:57:51Z
dc.date.issued2021-06
dc.description.abstractTuberculosis remains a leading cause of death, therapeutic failure being mainly due to non-compliance with prolonged treatments, often associated with severe side-effects. New therapeutic strategies are demanded and, considering that the lung is the primary site of infection, direct lung delivery of antibiotics is possibly an effective approach. Therapeutic success in this context depends on suitable carriers that reach the alveoli where Mycobacterium hosts (macrophages) reside, as well as on their ability to promote macrophage capture and intracellular accumulation of drugs. In this work, we propose inhalable polymeric microparticles produced from chondroitin sulfate, a polymer composed by moieties recognized by macrophage receptors. Spray-drying of chondroitin sulfate in combination with two first-line antitubercular drugs (isoniazid and rifabutin) yielded respirable microparticles that evidenced no cytotoxic effects on lung epithelial cells (A549) and macrophages (dTHP1 and J744A.1). The microparticles exhibited tendency for macrophage capture in a dose-dependent manner, which was validated through imaging. High content image analysis revealed that rifabutin induced a dose-dependent increase in phospholipid content of macrophages, which could be prevented by formulation in chondroitin sulfate microparticles. This work provides indications on the potential of chondroitin sulfate carriers to interact with macrophages, thus providing a platform for drug delivery in the context of macrophage intracellular diseases, namely tuberculosis.
dc.identifier.doi10.1016/j.ejpb.2021.04.001
dc.identifier.issn0939-6411
dc.identifier.urihttp://hdl.handle.net/10400.1/16954
dc.language.isoeng
dc.peerreviewedyes
dc.publisherELSEVIER
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.subjectAlveolar macrophages
dc.subjectAntitubercular drugs
dc.subjectChondroitin sulfate
dc.subjectMacrophage activation
dc.subjectToxicological profile
dc.subject.otherPharmacology & Pharmacy
dc.titleCytocompatibility and cellular interactions of chondroitin sulfate microparticles designed for inhaled tuberculosis treatment
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/6817 - DCRRNI ID/157544/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/36993/PT
oaire.citation.endPage178
oaire.citation.startPage171
oaire.citation.titleEuropean Journal of Pharmaceutics and Biopharmaceutics
oaire.citation.volume163
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
person.familyNameRodrigues
person.familyNameCunha
person.familyNameRosa da Costa
person.familyNameGrenha
person.givenNameSusana
person.givenNameLudmylla Costa
person.givenNameAna M
person.givenNameAna
person.identifier305029
person.identifier.ciencia-id9D1A-6537-0383
person.identifier.ciencia-idA418-A85E-5DB1
person.identifier.ciencia-id091C-0D58-7225
person.identifier.orcid0000-0002-0329-4265
person.identifier.orcid0000-0003-2620-5760
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-id53986075100
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.rightsrestrictedAccess
rcaap.typearticle
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