Publicação
Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection
| Resumo: | Tuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96. |
|---|---|
| Autores principais: | Grenha, Ana |
| Outros Autores: | Alves, Ana D.; Guerreiro, Filipa; Pinho, Jacinta; Simões, Sandra; Almeida, António José; Gaspar, Maria Manuela |
| Assunto: | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade do Algarve |
| Idioma: | inglês |
| Origem: | Sapientia - Universidade do Algarve |
| _version_ | 1867050896915955712 |
|---|---|
| author | Grenha, Ana |
| author2 | Alves, Ana D. Guerreiro, Filipa Pinho, Jacinta Simões, Sandra Almeida, António José Gaspar, Maria Manuela |
| author2_role | author author author author author author |
| author_facet | Grenha, Ana Alves, Ana D. Guerreiro, Filipa Pinho, Jacinta Simões, Sandra Almeida, António José Gaspar, Maria Manuela |
| author_role | author |
| contributor_name_str_mv | Sapientia |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Grenha, Ana\",\"Person.identifier.orcid\":\"0000-0002-2136-1396\"},{\"Person.name\":\"Alves, Ana D.\"},{\"Person.name\":\"Guerreiro, Filipa\",\"Person.identifier.orcid\":\"0000-0001-6224-1553\"},{\"Person.name\":\"Pinho, Jacinta\"},{\"Person.name\":\"Simões, Sandra\"},{\"Person.name\":\"Almeida, António José\"},{\"Person.name\":\"Gaspar, Maria Manuela\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Sapientia |
| datacite.creators.creator.creatorName.fl_str_mv | Grenha, Ana Alves, Ana D. Guerreiro, Filipa Pinho, Jacinta Simões, Sandra Almeida, António José Gaspar, Maria Manuela |
| datacite.date.Accepted.fl_str_mv | 2020-02-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2021-02-01T01:30:14Z |
| datacite.date.embargoed.fl_str_mv | 2021-02-01T01:30:14Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| datacite.titles.title.fl_str_mv | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| dc.contributor.none.fl_str_mv | Sapientia |
| dc.creator.none.fl_str_mv | Grenha, Ana Alves, Ana D. Guerreiro, Filipa Pinho, Jacinta Simões, Sandra Almeida, António José Gaspar, Maria Manuela |
| dc.date.Accepted.fl_str_mv | 2020-02-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2021-02-01T01:30:14Z |
| dc.date.embargoed.fl_str_mv | 2021-02-01T01:30:14Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.1/13683 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| dc.title.fl_str_mv | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Tuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://sapientia.ualg.pt/bitstreams/3fc3f819-2be8-45da-b6ca-0a82b995d39c/download |
| funding.funder.alternateName_str_mv | FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | 3599-PPCDT |
| id | sapientia_ca6cb2c4610276fa187a5cd9f3bdd9a0 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.1/13683 |
| instacron_str | ualg |
| institution | Universidade do Algarve |
| instname_str | Universidade do Algarve |
| language | eng |
| network_acronym_str | sapientia |
| network_name_str | Sapientia - Universidade do Algarve |
| oai_identifier_str | oai:sapientia.ualg.pt:10400.1/13683 |
| organization_str_mv | urn:organizationAcronym:ualg |
| person_str_mv | Grenha, Ana Grenha, Ana https://www.ciencia-id.pt/091C-0D58-7225 091C-0D58-7225 http://orcid.org/0000-0002-2136-1396 0000-0002-2136-1396 Alves, Ana D. Guerreiro, Filipa Guerreiro, Filipa https://www.ciencia-id.pt/BF1D-7EFA-19BC BF1D-7EFA-19BC http://orcid.org/0000-0001-6224-1553 0000-0001-6224-1553 Pinho, Jacinta Simões, Sandra Almeida, António José Gaspar, Maria Manuela |
| publishDate | 2020 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Sapientia - Universidade do Algarve |
| repository_id_str | urn:repositoryAcronym:sapientia |
| service_str_mv | urn:repositoryAcronym:sapientia |
| spelling | engElsevierpt_PTTuberculosis is a leading cause of death worldwide. Although the development of new antimycobacterial drugs is an obvious and necessary strategy to address the disease, improving the therapeutic performance of drugs already approved constitutes a valuable alternative approach. As the lung is the most affected organ, where M. tuberculosis is able to survive and proliferate, the direct pulmonary delivery of antitubercular drugs comprises a highly promising therapeutic strategy. In this work, spray-dried locust bean gum (LBG) microparticles were used to deliver a combination of two first line antitubercular drugs, isoniazid (INH) and rifabutin (RFB), to the alveolar zone, where macrophages hosting the bacteria reside. LBG is expected to mediate favoured macrophage uptake of microparticles, leading to enhanced therapeutic effect. The therapeutic effect of LBG/INH/RFB microparticles was evaluated in a murine model infected with M. tuberculosis, strain H37Rv and compared with oral co-therapy of INH and RFB in the free form. The pulmonary administration of LBG/INH/RFB microparticles 5 times per week was the only treatment schedule that provided negative growth index values in lung (-0.22), spleen (-0.14) and liver (-0.26) even using a lower therapeutic dose for both antibiotics. For the control group, the respective values were +1.95, +0.75 and +0.96.application/pdfpt_PTInhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infectionPersonalGrenha, AnaDSpacehttp://dspace.org/items/1bd4d8f1-40e5-45af-b1e8-4b8e73a6a70dDSpacehttp://dspace.org/items/1bd4d8f1-40e5-45af-b1e8-4b8e73a6a70dGrenhaAnaCiência IDhttps://www.ciencia-id.pt091C-0D58-7225ORCIDhttp://orcid.org0000-0002-2136-1396Researcher IDhttps://www.researcherid.comH-1392-2017Scopus Author IDhttps://www.scopus.com8607930100Alves, Ana D.PersonalGuerreiro, FilipaDSpacehttp://dspace.org/items/b88abfe8-e32c-477f-9fb0-5bdeca8a1a05DSpacehttp://dspace.org/items/b88abfe8-e32c-477f-9fb0-5bdeca8a1a05GuerreiroFilipaCiência IDhttps://www.ciencia-id.ptBF1D-7EFA-19BCORCIDhttp://orcid.org0000-0001-6224-1553Pinho, JacintaSimões, SandraAlmeida, António JoséGaspar, Maria ManuelaHostingInstitutionOrganizationalSapientiae-mailmailto:repositorio@ualg.ptrepositorio@ualg.ptISSNIsPartOf0939-6411DOIIsPartOf10.1016/j.ejpb.2019.11.0092021-02-01T01:30:14Z2020-022020-02-01T00:00:00ZHandlehttp://hdl.handle.net/10400.1/13683http://purl.org/coar/access_right/c_16ecrestricted accessTuberculosisPulmonary deliveryLocust bean gumSpray-dried microparticlesRifabutin; isoniazidIn vivo studies550262 bytesFundação para a Ciência e a TecnologiaFighting TB: Development of microparticulate systems to target alveolar macrophages in tuberculosis therapy3599-PPCDTCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaKonjac glucomannan microcarriers: an application in the treatment of pulmonary tuberculosisCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://sapientia.ualg.pt/bitstreams/3fc3f819-2be8-45da-b6ca-0a82b995d39c/downloadEuropean Journal of Pharmaceutics and Biopharmaceutics1473844 |
| spellingShingle | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection Grenha, Ana Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| status | SINGLETON |
| subject.fl_str_mv | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| title | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| title_full | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| title_fullStr | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| title_full_unstemmed | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| title_short | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| title_sort | Inhalable locust bean gum microparticles co-associating isoniazid and rifabutin: therapeutic assessment in a murine model of tuberculosis infection |
| topic | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| topic_facet | Tuberculosis Pulmonary delivery Locust bean gum Spray-dried microparticles Rifabutin; isoniazid In vivo studies |
| url | http://hdl.handle.net/10400.1/13683 |
| visible | 1 |