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Inhalable chitosan microparticles as tools in tuberculosis therapy

2017-08Conference object Restricted
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dc.contributor.authorCunha, Jose C.
dc.contributor.authorCosta, Ana M Rosa Da
dc.contributor.authorGrenha, Ana
dc.date.accessioned2019-11-20T15:07:27Z
dc.date.available2019-11-20T15:07:27Z
dc.date.issued2017-08
dc.description.abstractLung tuberculosis (TB) represents approximately 80% of total cases and, therefore, the lung has been explored as an effective route for the delivery of drugs in the ambit of pulmonary TB. The pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognized and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Chitosan (CS) is a polysaccharide composed of N-acetylglucosamine and D-glucosamine residues, the former being recognised by macrophages and possibly potentiating phagocytosis. This work aimed at producing chitosan microparticles (CS MP) containing two first-line antitubercular drugs, isoniazid (INH) and rifabutin (RFB). A polymeric solution containing 10% (w/w) of INH and 5% (w/w) RFB (weight respective to CS), was spray-dried and the resulting microparticles evaluated as inhalable dry powder inhalation targeting alveolar macrophages. Spray-dried CS MP with theoretically adequate properties for deep lung delivery (aerodynamic diameter of 1.98 μm) were produced, efficiently associating isoniazid (INH) and rifabutin (RFB) – 73% and 97%, respectively – in combination. The effect of drug-loaded CS MP on the viability of two cell lines representative of the environment of relevance in pulmonary TB were assessed and absence of toxicity was observed in human alveolar epithelium (A549) and macrophage-differentiated (THP-1) cells. Human macrophage-differentiated THP-1 cells and rat alveolar macrophages NR8383 were exposed to fluorescein-labelled CS MP to assess the ability of CS MP to be taken up by alveolar macrophages. The analysis was performed by flow cytometry and CS MP evidenced strong ability to be captured by macrophages (percentage of phagocytosis >98%). Overall, the obtained data gave positive indications on the potential of the proposed system for an application as inhalable tuberculosis therapy.
dc.identifier.issn1941-2711
dc.identifier.issn1941-2703
dc.identifier.urihttp://hdl.handle.net/10400.1/13051
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMary Ann Liebert
dc.relationFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy
dc.titleInhalable chitosan microparticles as tools in tuberculosis therapy
dc.typeconference object
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.endPageA15
oaire.citation.issue4
oaire.citation.startPageA15
oaire.citation.titleJournal of Aerosol Medicine and Pulmonary Drug Delivery
oaire.citation.volume30
oaire.fundingStream3599-PPCDT
oaire.fundingStream5876
oaire.fundingStream5876
person.familyNameCunha
person.familyNameRosa da Costa
person.familyNameGrenha
person.givenNameJose Alberto C.
person.givenNameAna M
person.givenNameAna
person.identifier305029
person.identifier.ciencia-idA418-A85E-5DB1
person.identifier.ciencia-id091C-0D58-7225
person.identifier.orcid0000-0001-6729-8348
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-id7102903739
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.typeconferenceObject
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