Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis
Autor(a) principal: | |
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Data de Publicação: | 2008 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/61465 |
Resumo: | Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of antimycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24h post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidylglycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients. |
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Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosisAnimalsAntitubercular AgentsChemistry, PharmaceuticalLiposomesLiverLungMiceMice, Inbred BALB CRifabutinSpleenTime FactorsTuberculosisHIV/AIDS patientsdrug deliveryCiências Médicas::Medicina BásicaScience & TechnologyTuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of antimycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24h post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidylglycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients.This work was supported by grants from FCT (POCTI/FCB/36416/99) and from the Health Services of FCG. Fellowships were granted by FCT (SFRH/BD/9624/2002- GABBA Program to A. Cruz and SFRH/BD/15911/2005 to A.G. Fraga)ElsevierUniversidade do MinhoGaspar, M. M.Cruz, A.Penha, A. F.Reymão, J.Sousa, A. C.Eleutério, C. V.Domingues, S. A.Fraga, A. G.Longatto, AdhemarCruz, M. E. M.Pedrosa, Jorge2008-012008-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/61465engGaspar, M. M., Cruz, A., Penha, A. F., Reymao, J., Sousa, A. C., Eleutério, C. V., ... & Pedrosa, J. (2008). Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis. International journal of antimicrobial agents, 31(1), 37-450924-85791872-791310.1016/j.ijantimicag.2007.08.00818006283https://www.sciencedirect.com/science/article/pii/S0924857907004165info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:19:27Zoai:repositorium.sdum.uminho.pt:1822/61465Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:12:23.447604Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
title |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
spellingShingle |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis Gaspar, M. M. Animals Antitubercular Agents Chemistry, Pharmaceutical Liposomes Liver Lung Mice Mice, Inbred BALB C Rifabutin Spleen Time Factors Tuberculosis HIV/AIDS patients drug delivery Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
title_full |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
title_fullStr |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
title_full_unstemmed |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
title_sort |
Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis |
author |
Gaspar, M. M. |
author_facet |
Gaspar, M. M. Cruz, A. Penha, A. F. Reymão, J. Sousa, A. C. Eleutério, C. V. Domingues, S. A. Fraga, A. G. Longatto, Adhemar Cruz, M. E. M. Pedrosa, Jorge |
author_role |
author |
author2 |
Cruz, A. Penha, A. F. Reymão, J. Sousa, A. C. Eleutério, C. V. Domingues, S. A. Fraga, A. G. Longatto, Adhemar Cruz, M. E. M. Pedrosa, Jorge |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Gaspar, M. M. Cruz, A. Penha, A. F. Reymão, J. Sousa, A. C. Eleutério, C. V. Domingues, S. A. Fraga, A. G. Longatto, Adhemar Cruz, M. E. M. Pedrosa, Jorge |
dc.subject.por.fl_str_mv |
Animals Antitubercular Agents Chemistry, Pharmaceutical Liposomes Liver Lung Mice Mice, Inbred BALB C Rifabutin Spleen Time Factors Tuberculosis HIV/AIDS patients drug delivery Ciências Médicas::Medicina Básica Science & Technology |
topic |
Animals Antitubercular Agents Chemistry, Pharmaceutical Liposomes Liver Lung Mice Mice, Inbred BALB C Rifabutin Spleen Time Factors Tuberculosis HIV/AIDS patients drug delivery Ciências Médicas::Medicina Básica Science & Technology |
description |
Tuberculosis (TB) is a leading cause of death amongst infectious diseases. The low permeation of antimycobacterial agents and their difficult access to infected macrophages necessitate long-term use of high drug doses. Liposomes preferentially accumulate in macrophages, increasing the efficacy of antibiotics against intracellular parasites. In the present work, several rifabutin (RFB) liposomal formulations were developed and characterised and their in vivo profile was compared with free RFB following intravenous administration. With the RFB liposomal formulations tested, higher concentrations of the antibiotic were achieved in liver, spleen and lungs 24h post administration compared with free RFB. The concentration of RFB in these organs was dependent on the rigidity of liposomal lipids. The liposomal RFB formulation prepared with dipalmitoyl phosphatidylcholine:dipalmitoyl phosphatidylglycerol (DPPC:DPPG) was the most effective and was selected for biological evaluation in a mouse model of disseminated TB. Compared with mice treated with free RFB, mice treated with the DPPC:DPPG RFB formulation exhibited lower bacterial loads in the spleen (5.53 log(10) vs. 5.18 log(10)) and liver (5.79 log(10) vs. 5.41 log(10)). In the lung, the level of pathology was lower in mice treated with encapsulated RFB. These results suggest that liposomal RFB is a promising approach for the treatment of extrapulmonary TB in human immunodeficiency virus co-infected patients. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-01 2008-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/61465 |
url |
http://hdl.handle.net/1822/61465 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Gaspar, M. M., Cruz, A., Penha, A. F., Reymao, J., Sousa, A. C., Eleutério, C. V., ... & Pedrosa, J. (2008). Rifabutin encapsulated in liposomes exhibits increased therapeutic activity in a model of disseminated tuberculosis. International journal of antimicrobial agents, 31(1), 37-45 0924-8579 1872-7913 10.1016/j.ijantimicag.2007.08.008 18006283 https://www.sciencedirect.com/science/article/pii/S0924857907004165 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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