Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood

Detalhes bibliográficos
Autor(a) principal: Sousa, Vera Catarina Ferreira de
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/28437
Resumo: Blood is an essential body fluid but is yet a source of microbial infections transmission. Consequently, the ability to disinfect blood and its derivatives has assumed great importance. Currently, the most used method for inactivating microorganisms, which can be only used in plasma or protein concentrates, is the combined use of a tri(n-butyl)phosphate and the detergent Tween 80. However, these chemicals must be removed after disinfection procedure once they are harmful to the membranes of erythrocytes and platelets of blood receptors. Antimicrobial Photodynamic Therapy (aPDT) has been suggested as an alternative technique to blood disinfection. Methylene blue (MB), psoralen and riboflavin are already approved photosensitizers (PS) in some countries to disinfect plasma/platelets, but there is no aPDT approved application for whole blood and erythrocytes concentrates. The aim of this study was to evaluate the effectiveness of aPDT to inactivate Candida albicans in blood, a microorganism frequently involved in bloodstream infections. For that, several cationic porphyrin derivatives were used to photoinactivate C. albicans in phosphate buffered saline (PBS), plasma and whole blood. Once MB is the mostly used PS to disinfect plasma, its efficacy was also evaluated for comparison. Samples and controls were exposed for 270 min to white light (380-700 nm) at an irradiance of 2.5 mW/cm2 and 150 mW/cm2 for PBS and whole blood/plasma, respectively. All the tested cationic porphyrin derivatives were effective to photoinactivate C. albicans in PBS. However, MB under the same conditions (concentration and light dose) did not appear to be efficient in C. albicans inactivation. In plasma, FORM and Tri-Py(+)-Me proved to be promising PSs in C. albicans photoinactivation. Although in whole blood the inactivation rates obtained with porphyrin derivatives were higher than the ones obtained with MB, further improvements are required. Nevertheless, the results indicate that aPDT using cationic porphyrinic photosensitizers seems to be a promising approach for the photoinactivation of C. albicans in plasma. Additionally, none of these PSs, in the tested concentrations in plasma and whole blood, had promoted significant hemolysis at the isotonic conditions when hemolysis was evaluated in whole blood and after the addition of aPDT treated plasma with these PSs to concentrated erythrocytes.
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spelling Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in bloodAntimicrobial Photodynamic TherapyCandida albicansCationic porphyrinsMethylene blueBlood plasmaWhole bloodPhotosensitizerBlood is an essential body fluid but is yet a source of microbial infections transmission. Consequently, the ability to disinfect blood and its derivatives has assumed great importance. Currently, the most used method for inactivating microorganisms, which can be only used in plasma or protein concentrates, is the combined use of a tri(n-butyl)phosphate and the detergent Tween 80. However, these chemicals must be removed after disinfection procedure once they are harmful to the membranes of erythrocytes and platelets of blood receptors. Antimicrobial Photodynamic Therapy (aPDT) has been suggested as an alternative technique to blood disinfection. Methylene blue (MB), psoralen and riboflavin are already approved photosensitizers (PS) in some countries to disinfect plasma/platelets, but there is no aPDT approved application for whole blood and erythrocytes concentrates. The aim of this study was to evaluate the effectiveness of aPDT to inactivate Candida albicans in blood, a microorganism frequently involved in bloodstream infections. For that, several cationic porphyrin derivatives were used to photoinactivate C. albicans in phosphate buffered saline (PBS), plasma and whole blood. Once MB is the mostly used PS to disinfect plasma, its efficacy was also evaluated for comparison. Samples and controls were exposed for 270 min to white light (380-700 nm) at an irradiance of 2.5 mW/cm2 and 150 mW/cm2 for PBS and whole blood/plasma, respectively. All the tested cationic porphyrin derivatives were effective to photoinactivate C. albicans in PBS. However, MB under the same conditions (concentration and light dose) did not appear to be efficient in C. albicans inactivation. In plasma, FORM and Tri-Py(+)-Me proved to be promising PSs in C. albicans photoinactivation. Although in whole blood the inactivation rates obtained with porphyrin derivatives were higher than the ones obtained with MB, further improvements are required. Nevertheless, the results indicate that aPDT using cationic porphyrinic photosensitizers seems to be a promising approach for the photoinactivation of C. albicans in plasma. Additionally, none of these PSs, in the tested concentrations in plasma and whole blood, had promoted significant hemolysis at the isotonic conditions when hemolysis was evaluated in whole blood and after the addition of aPDT treated plasma with these PSs to concentrated erythrocytes.O sangue é um recurso essencial, porém também é uma fonte de transmissão de infeções. Consequentemente, a capacidade de desinfetar o sangue e seus derivados assume uma grande importância na prática clínica. Atualmente, o método de desinfeção mais eficaz na inativação de microrganismos usado apenas em plasma e concentrados proteicos, baseia-se no uso combinado do tri(n-butil)fosfato e do detergente Tween 80. No entanto, estes produtos devem ser removidos após o procedimento de desinfeção, pois são prejudiciais quer para as membranas dos eritrócitos quer para as plaquetas dos indivíduos transfundidos. A Terapia Fotodinâmica Antimicrobiana (aPDT) tem sido sugerida como uma técnica alternativa à desinfeção do sangue. Os fotossensibilizadores (PS) azul-de-metileno (MB), derivados de psoraleno e riboflavina já se encontram aprovados em alguns países para desinfetar plasma e plaquetas, no entanto não há até à data nenhuma aplicação aprovada baseada em aPDT para a desinfeção de sangue total e de concentrados de eritrócitos. O objetivo deste estudo foi avaliar a eficácia da aPDT na inativação de Candida albicans, um microorganismo frequentemente envolvido em infeções sistémicas. Para isso, foram usados derivados porfirínicos catiónicos na fotoinativação de C. albicans em tampão fosfato-salino (PBS), plasma e sangue total. Uma vez que o MB é o PS mais usado para desinfetar plasma, a sua eficácia também foi avaliada para comparar com a eficiência dos derivados porfirínicos testados. As amostras e os controlos foram expostos durante 270 min a luz branca (380-700 nm) com uma irradiação de 2,5 e 150 mW/cm2 para PBS e sangue total / plasma, respetivamente. Todos os derivados porfirínicos catiónicos testados foram eficazes na fotoinativação de C. albicans em PBS, no entanto, o MB nas mesmas condições (concentração e dose de luz) não demonstrou possuir capacidade de inativar C. albicans. No plasma, a FORM e Tri-Py(+)-Me provaram ser fotossensibilizadores promissores na inativação de C. albicans. Apesar de no sangue total as taxas de fotoinativação obtidas com os fotossensibilizadores porfirínicos tenham sido mais altas que as obtidas com MB, mais estudos serão necessários para melhorar as taxas de inativação obtidas. No entanto, os resultados indicam que a aPDT usando fotossensibilizadores porfirínicos catiónicos parece ser uma abordagem promissora para a fotoinativação de C. albicans no plasma. Destaca-se o facto que nenhum destes fotossensibilizadores porfirínicos nas concentrações testadas no plasma e no sangue total promoveu hemólise significativa em condições isotónicas. Uma situação similar foi observada quando foi avaliada a hemólise após a adição de plasma tratado com esses PSs a concentrados de eritrócitos.2019-122019-12-01T00:00:00Z2020-12-20T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/28437engSousa, Vera Catarina Ferreira deinfo: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:RCAAP2024-02-22T11:55:01Zoai:ria.ua.pt:10773/28437Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:00:59.141887Repositório 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 Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
title Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
spellingShingle Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
Sousa, Vera Catarina Ferreira de
Antimicrobial Photodynamic Therapy
Candida albicans
Cationic porphyrins
Methylene blue
Blood plasma
Whole blood
Photosensitizer
title_short Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
title_full Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
title_fullStr Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
title_full_unstemmed Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
title_sort Cationic porphyrinic photosensitizers in the inactivation of Candida albicans in blood
author Sousa, Vera Catarina Ferreira de
author_facet Sousa, Vera Catarina Ferreira de
author_role author
dc.contributor.author.fl_str_mv Sousa, Vera Catarina Ferreira de
dc.subject.por.fl_str_mv Antimicrobial Photodynamic Therapy
Candida albicans
Cationic porphyrins
Methylene blue
Blood plasma
Whole blood
Photosensitizer
topic Antimicrobial Photodynamic Therapy
Candida albicans
Cationic porphyrins
Methylene blue
Blood plasma
Whole blood
Photosensitizer
description Blood is an essential body fluid but is yet a source of microbial infections transmission. Consequently, the ability to disinfect blood and its derivatives has assumed great importance. Currently, the most used method for inactivating microorganisms, which can be only used in plasma or protein concentrates, is the combined use of a tri(n-butyl)phosphate and the detergent Tween 80. However, these chemicals must be removed after disinfection procedure once they are harmful to the membranes of erythrocytes and platelets of blood receptors. Antimicrobial Photodynamic Therapy (aPDT) has been suggested as an alternative technique to blood disinfection. Methylene blue (MB), psoralen and riboflavin are already approved photosensitizers (PS) in some countries to disinfect plasma/platelets, but there is no aPDT approved application for whole blood and erythrocytes concentrates. The aim of this study was to evaluate the effectiveness of aPDT to inactivate Candida albicans in blood, a microorganism frequently involved in bloodstream infections. For that, several cationic porphyrin derivatives were used to photoinactivate C. albicans in phosphate buffered saline (PBS), plasma and whole blood. Once MB is the mostly used PS to disinfect plasma, its efficacy was also evaluated for comparison. Samples and controls were exposed for 270 min to white light (380-700 nm) at an irradiance of 2.5 mW/cm2 and 150 mW/cm2 for PBS and whole blood/plasma, respectively. All the tested cationic porphyrin derivatives were effective to photoinactivate C. albicans in PBS. However, MB under the same conditions (concentration and light dose) did not appear to be efficient in C. albicans inactivation. In plasma, FORM and Tri-Py(+)-Me proved to be promising PSs in C. albicans photoinactivation. Although in whole blood the inactivation rates obtained with porphyrin derivatives were higher than the ones obtained with MB, further improvements are required. Nevertheless, the results indicate that aPDT using cationic porphyrinic photosensitizers seems to be a promising approach for the photoinactivation of C. albicans in plasma. Additionally, none of these PSs, in the tested concentrations in plasma and whole blood, had promoted significant hemolysis at the isotonic conditions when hemolysis was evaluated in whole blood and after the addition of aPDT treated plasma with these PSs to concentrated erythrocytes.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
2019-12-01T00:00:00Z
2020-12-20T00:00:00Z
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