Publication
Chondroitin sulphate microparticles for tuberculosis treatment: a way to target macrophages
| dc.contributor.author | Rodrigues, Susana | |
| dc.contributor.author | Rosa Da Costa, Ana | |
| dc.contributor.author | Grenha, Ana | |
| dc.date.accessioned | 2019-11-20T15:07:28Z | |
| dc.date.available | 2019-11-20T15:07:28Z | |
| dc.date.issued | 2017-08 | |
| dc.description.abstract | Tuberculosis 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 an interesting and, possibly, 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 chondroitin sulphate microparticles produced by spray-drying and tailored to suitable aerodynamic properties to reach the alveoli. Macrophage targeting will be driven by microparticle size, which is favoured for carriers of 1-2 μm, and composition based on chondroitin sulphate, a glycosaminoglycan comprised of alternating units of sulphated N-acetylgalactosamine and glucuronic acid residues, the former recognized by macrophage receptors. Spray-drying of chondroitin sulphate in combination with two first-line antitubercular drugs (isoniazid and rifabutin) was successful with a satisfactory production yield (> 70%). Microparticles have Feret’s diameter of 1.6 μm, potentiating macrophage uptake. Chondroitin sulphate as solution or microparticulate form and drug-loaded microparticles appear to not have a cytotoxic effect on alveolar epithelial cells. A more extended biocompatibility/safety assessment of this formulation needs to be performed. Taking into account the general trend of the results obtained so far, good indications are given that encourage the continuation of the studies in order to establish the potential of these microparticles as inhalable carriers in tuberculosis treatment. | |
| dc.identifier.issn | 1941-2711 | |
| dc.identifier.issn | 1941-2703 | |
| dc.identifier.uri | http://hdl.handle.net/10400.1/13053 | |
| dc.language.iso | eng | |
| dc.peerreviewed | yes | |
| dc.publisher | Mary Ann Liebert, Inc | |
| dc.relation | SFRH/BD/52426/2013 | |
| dc.relation | Fighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy | |
| dc.title | Chondroitin sulphate microparticles for tuberculosis treatment: a way to target macrophages | |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.awardTitle | Fighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F0094%2F2012/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FMulti%2F04326%2F2013/PT | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F04773%2F2013/PT | |
| oaire.citation.endPage | A22 | |
| oaire.citation.issue | 4 | |
| oaire.citation.startPage | A21 | |
| oaire.citation.title | Journal of Aerosol Medicine and Pulmonary Drug Delivery | |
| oaire.citation.volume | 30 | |
| oaire.fundingStream | 3599-PPCDT | |
| oaire.fundingStream | 5876 | |
| oaire.fundingStream | 5876 | |
| person.familyName | Rodrigues | |
| person.familyName | Rosa da Costa | |
| person.familyName | Grenha | |
| person.givenName | Susana | |
| person.givenName | Ana M | |
| person.givenName | Ana | |
| person.identifier | 305029 | |
| person.identifier.ciencia-id | 9D1A-6537-0383 | |
| person.identifier.ciencia-id | A418-A85E-5DB1 | |
| person.identifier.ciencia-id | 091C-0D58-7225 | |
| person.identifier.orcid | 0000-0002-0329-4265 | |
| person.identifier.orcid | 0000-0003-0225-9537 | |
| person.identifier.orcid | 0000-0002-2136-1396 | |
| person.identifier.rid | E-2165-2012 | |
| person.identifier.rid | H-1392-2017 | |
| person.identifier.scopus-author-id | 55125292100 | |
| person.identifier.scopus-author-id | 53986075100 | |
| person.identifier.scopus-author-id | 8607930100 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | restrictedAccess | |
| rcaap.type | conferenceObject | |
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