Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/34870 |
Resumo: | American Cutaneous Leishmaniasis (ACL) is a polymorphic disease of the skin and mucosa caused by the parasite of the genus Leishmania. Treatment options have limitations, especially toxicity and drug esistance,compromising the safety and efficacy of the therapy. The search for a topical treatment is recommended by the WHO. Amphotericin B (Anf- B) is a polyene antibiotic, already used in the treatment of ACL in the form of intravenous lipid preparations, including liposomes. Sodium chlorite (NaClO2) has been nvestigated for its oxidative potential and healing action on lesions caused by L. tropica. OBJECTIVE. The present work investigates the potential of the Anf-B / NaClO2 association as a basis for a new treatment of LTA from topical nanoformulations containing these agents. MATERIAL AND METHODS. The NaClO2 and Anf-B cytotoxicity assays were performed against axenic promastigotes of L. braziliensis (MHOM / BR / 01 / BA788) for IC50 determination of these compounds. To evaluate the combined effect, NaClO2 and Anf-B were tested according to the modified fixed ratio method (1: 1, 1: 5, 5: 1). In addition, the cell viability of peritoneal macrophages of BALB / c mice and human keratinocytes (HaCaT) was evaluated in the presence of each individual treatment and CC50 was calculated. These tests were performed using Alamar blue® colorimetric method. NaClO2 activity was evaluated alone and in Combination with Anf-B on L.braziliensis-infected macrophages. The activity of NaClO2 was evaluated on the viability of axenic amastigotes of L.braziliensis, using the colorimetric method of Alamar blue®. SEM and TEM images were obtained from promastigotes and axenic amastigotes treated with 14 ìM NaClO2. Semisolid formulations were developed containing Anf-B in solid lipid nanoparticles (NLS) and free. In vitro release study of the drug in Franz cells was performed for a period of 12 hours (0, 30min, 1h, 2h, 4h, 6h, 8h and 12h). Stability studies of these formulations were performed over a period of 14 days. RESULTS. The results demonstrate that NaClO2 and Anf-B presented a mean IC50 of 9.66 ìM and 0.11 ìM,respectively, on the romastigote forms after 72 h of culture. SEM and TEM images suggest na activity on the increase of oxidative stress of NaClO2 on promastigotes. The combination of the two compounds resulted in an additive effect with na average combination index of 0.98 ± 0.09.Regarding cell viability assays, NaClO2 and Anf-B presented CC50 values of 856.3 ìM and> 50 ìM, respectively. The selectivity index of NaClO2 was estimated at 88.6 and Anf-B> 454.5.NaClO2 showed no activity on the viability of intracellular and extracellular amastigotes, which was reinforced by SEM and TEM images. In vitro release studies on Franz cells demonstrated that Anf-B was released more slowly and gradually when in a nanostructured system and all formulations remained stable over 14 days. CONCLUSIONS. For the first time, this work demonstrated the activity of NaClO2 in New World Leishmania. Additionally, it presented the pharmacotechnical potential of nanoformulations containing Anf-B for the treatment of ACL. |
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Magalhães, Carla PiresMoreira, Diogo Rodrigo de MagalhãesPires, Acássía Benjamim Leal PiresTavares, Natália MachadoFormiga, Fabio Rocha2019-08-19T13:13:00Z2019-08-19T13:13:00Z2018MAGALHAES, Carla Pires. Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose tegumentar. 2018. 101 f. Mestrado (Dissertação em Biotecnologia Biotecnologia em Saúde e Medicina Investigativa) - Instituto de Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2018.https://www.arca.fiocruz.br/handle/icict/34870American Cutaneous Leishmaniasis (ACL) is a polymorphic disease of the skin and mucosa caused by the parasite of the genus Leishmania. Treatment options have limitations, especially toxicity and drug esistance,compromising the safety and efficacy of the therapy. The search for a topical treatment is recommended by the WHO. Amphotericin B (Anf- B) is a polyene antibiotic, already used in the treatment of ACL in the form of intravenous lipid preparations, including liposomes. Sodium chlorite (NaClO2) has been nvestigated for its oxidative potential and healing action on lesions caused by L. tropica. OBJECTIVE. The present work investigates the potential of the Anf-B / NaClO2 association as a basis for a new treatment of LTA from topical nanoformulations containing these agents. MATERIAL AND METHODS. The NaClO2 and Anf-B cytotoxicity assays were performed against axenic promastigotes of L. braziliensis (MHOM / BR / 01 / BA788) for IC50 determination of these compounds. To evaluate the combined effect, NaClO2 and Anf-B were tested according to the modified fixed ratio method (1: 1, 1: 5, 5: 1). In addition, the cell viability of peritoneal macrophages of BALB / c mice and human keratinocytes (HaCaT) was evaluated in the presence of each individual treatment and CC50 was calculated. These tests were performed using Alamar blue® colorimetric method. NaClO2 activity was evaluated alone and in Combination with Anf-B on L.braziliensis-infected macrophages. The activity of NaClO2 was evaluated on the viability of axenic amastigotes of L.braziliensis, using the colorimetric method of Alamar blue®. SEM and TEM images were obtained from promastigotes and axenic amastigotes treated with 14 ìM NaClO2. Semisolid formulations were developed containing Anf-B in solid lipid nanoparticles (NLS) and free. In vitro release study of the drug in Franz cells was performed for a period of 12 hours (0, 30min, 1h, 2h, 4h, 6h, 8h and 12h). Stability studies of these formulations were performed over a period of 14 days. RESULTS. The results demonstrate that NaClO2 and Anf-B presented a mean IC50 of 9.66 ìM and 0.11 ìM,respectively, on the romastigote forms after 72 h of culture. SEM and TEM images suggest na activity on the increase of oxidative stress of NaClO2 on promastigotes. The combination of the two compounds resulted in an additive effect with na average combination index of 0.98 ± 0.09.Regarding cell viability assays, NaClO2 and Anf-B presented CC50 values of 856.3 ìM and> 50 ìM, respectively. The selectivity index of NaClO2 was estimated at 88.6 and Anf-B> 454.5.NaClO2 showed no activity on the viability of intracellular and extracellular amastigotes, which was reinforced by SEM and TEM images. In vitro release studies on Franz cells demonstrated that Anf-B was released more slowly and gradually when in a nanostructured system and all formulations remained stable over 14 days. CONCLUSIONS. For the first time, this work demonstrated the activity of NaClO2 in New World Leishmania. Additionally, it presented the pharmacotechnical potential of nanoformulations containing Anf-B for the treatment of ACL.American Cutaneous Leishmaniasis (ACL) is a polymorphic disease of the skin and mucosa caused by the parasite of the genus Leishmania. Treatment options have limitations, especially toxicity and drug resistance, compromising the safety and efficacy of the therapy. The search for a topical treatment is recommended by the WHO. Amphotericin B (Anf-B) is a polyene antibiotic, already used in the treatment of ACL in the form of intravenous lipid preparations, including liposomes. Sodium chlorite (NaClO2) has been investigated for its oxidative potential and healing action on lesions caused by L. tropica. OBJECTIVE. The present work investigates the potential of the Anf-B / NaClO2 association as a basis for a new treatment of LTA from topical nanoformulations containing these agents. MATERIAL AND METHODS. The NaClO2 and Anf-B cytotoxicity assays were performed against axenic promastigotes of L. braziliensis (MHOM / BR / 01 / BA788) for IC50 determination of these compounds. To evaluate the combined effect, NaClO2 and Anf-B were tested according to the modified fixed ratio method (1: 1, 1: 5, 5: 1). In addition, the cell viability of peritoneal macrophages of BALB / c mice and human keratinocytes (HaCaT) was evaluated in the presence of each individual treatment and CC50 was calculated. These tests were performed using Alamar blue® colorimetric method. NaClO2 activity was evaluated alone and in combination with Anf-B on L.braziliensis-infected macrophages. The activity of NaClO2 was evaluated on the viability of axenic amastigotes of L.braziliensis, using the colorimetric method of Alamar blue®. SEM and TEM images were obtained from promastigotes and axenic amastigotes treated with 14 μM NaClO2. Semisolid formulations were developed containing Anf-B in solid lipid nanoparticles (NLS) and free. In vitro release study of the drug in Franz cells was performed for a period of 12 hours (0, 30min, 1h, 2h, 4h, 6h, 8h and 12h). Stability studies of these formulations were performed over a period of 14 days. RESULTS. The results demonstrate that NaClO2 and Anf-B presented a mean IC50 of 9.66 μM and 0.11 μM, respectively, on the promastigote forms after 72 h of culture. SEM and TEM images suggest an activity on the increase of oxidative stress of NaClO2 on promastigotes. The combination of the two compounds resulted in an additive effect with an average combination index of 0.98 ± 0.09. Regarding cell viability assays, NaClO2 and Anf-B presented CC50 values of 856.3 μM and> 50 μM, respectively. The selectivity index of NaClO2 was estimated at 88.6 and Anf-B> 454.5. NaClO2 showed no activity on the viability of intracellular and extracellular amastigotes, which was reinforced by SEM and TEM images. In vitro release studies on Franz cells demonstrated that Anf-B was released more slowly and gradually when in a nanostructured system and all formulations remained stable over 14 days. CONCLUSIONS. For the first time, this work demonstrated the activity of NaClO2 in New World Leishmania. Additionally, it presented the pharmacotechnical potential of nanoformulations containing Anf-B for the treatment of ACL.O presente trabalho foi realizado com apoio da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Código de Financiamento 001.Fundação Oswaldo Cruz. Fundação Gonçalo Moniz. Salvador, BA, Brasil.porInstituto Gonçalo MonizLeishmaniose cutâneaAnfotericinaCloreto de SódioNanotecnologiaCutaneous leishmaniasisAmphotericin BSodium chloriteNanotechnologyDesenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentarinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis2018-02-20Coordenação de EnsinoFundação Oswaldo Cruz. Instituto Gonçalo MonizMestrado AcadêmicoSalvador/BAPós-Graduação em Biotecnologia em Saúde e Medicina Investigativainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/34870/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALCarla Pires Magalhães. Desenvolvimento nanoformulações ...2019.pdfCarla Pires Magalhães. Desenvolvimento nanoformulações ...2019.pdfapplication/pdf1191515https://www.arca.fiocruz.br/bitstream/icict/34870/2/Carla%20Pires%20Magalh%c3%a3es.%20Desenvolvimento%20nanoformula%c3%a7%c3%b5es%20...2019.pdf68f158ad01fd22c26fe934cfc7062d0fMD52TEXTCarla Pires Magalhães. Desenvolvimento nanoformulações ...2019.pdf.txtCarla Pires Magalhães. 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dc.title.pt_BR.fl_str_mv |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
title |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
spellingShingle |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar Magalhães, Carla Pires Leishmaniose cutânea Anfotericina Cloreto de Sódio Nanotecnologia Cutaneous leishmaniasis Amphotericin B Sodium chlorite Nanotechnology |
title_short |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
title_full |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
title_fullStr |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
title_full_unstemmed |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
title_sort |
Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose Tegumentar |
author |
Magalhães, Carla Pires |
author_facet |
Magalhães, Carla Pires |
author_role |
author |
dc.contributor.member.none.fl_str_mv |
Moreira, Diogo Rodrigo de Magalhães Pires, Acássía Benjamim Leal Pires Tavares, Natália Machado |
dc.contributor.author.fl_str_mv |
Magalhães, Carla Pires |
dc.contributor.advisor1.fl_str_mv |
Formiga, Fabio Rocha |
contributor_str_mv |
Formiga, Fabio Rocha |
dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose cutânea Anfotericina Cloreto de Sódio Nanotecnologia |
topic |
Leishmaniose cutânea Anfotericina Cloreto de Sódio Nanotecnologia Cutaneous leishmaniasis Amphotericin B Sodium chlorite Nanotechnology |
dc.subject.en.pt_BR.fl_str_mv |
Cutaneous leishmaniasis Amphotericin B Sodium chlorite Nanotechnology |
description |
American Cutaneous Leishmaniasis (ACL) is a polymorphic disease of the skin and mucosa caused by the parasite of the genus Leishmania. Treatment options have limitations, especially toxicity and drug esistance,compromising the safety and efficacy of the therapy. The search for a topical treatment is recommended by the WHO. Amphotericin B (Anf- B) is a polyene antibiotic, already used in the treatment of ACL in the form of intravenous lipid preparations, including liposomes. Sodium chlorite (NaClO2) has been nvestigated for its oxidative potential and healing action on lesions caused by L. tropica. OBJECTIVE. The present work investigates the potential of the Anf-B / NaClO2 association as a basis for a new treatment of LTA from topical nanoformulations containing these agents. MATERIAL AND METHODS. The NaClO2 and Anf-B cytotoxicity assays were performed against axenic promastigotes of L. braziliensis (MHOM / BR / 01 / BA788) for IC50 determination of these compounds. To evaluate the combined effect, NaClO2 and Anf-B were tested according to the modified fixed ratio method (1: 1, 1: 5, 5: 1). In addition, the cell viability of peritoneal macrophages of BALB / c mice and human keratinocytes (HaCaT) was evaluated in the presence of each individual treatment and CC50 was calculated. These tests were performed using Alamar blue® colorimetric method. NaClO2 activity was evaluated alone and in Combination with Anf-B on L.braziliensis-infected macrophages. The activity of NaClO2 was evaluated on the viability of axenic amastigotes of L.braziliensis, using the colorimetric method of Alamar blue®. SEM and TEM images were obtained from promastigotes and axenic amastigotes treated with 14 ìM NaClO2. Semisolid formulations were developed containing Anf-B in solid lipid nanoparticles (NLS) and free. In vitro release study of the drug in Franz cells was performed for a period of 12 hours (0, 30min, 1h, 2h, 4h, 6h, 8h and 12h). Stability studies of these formulations were performed over a period of 14 days. RESULTS. The results demonstrate that NaClO2 and Anf-B presented a mean IC50 of 9.66 ìM and 0.11 ìM,respectively, on the romastigote forms after 72 h of culture. SEM and TEM images suggest na activity on the increase of oxidative stress of NaClO2 on promastigotes. The combination of the two compounds resulted in an additive effect with na average combination index of 0.98 ± 0.09.Regarding cell viability assays, NaClO2 and Anf-B presented CC50 values of 856.3 ìM and> 50 ìM, respectively. The selectivity index of NaClO2 was estimated at 88.6 and Anf-B> 454.5.NaClO2 showed no activity on the viability of intracellular and extracellular amastigotes, which was reinforced by SEM and TEM images. In vitro release studies on Franz cells demonstrated that Anf-B was released more slowly and gradually when in a nanostructured system and all formulations remained stable over 14 days. CONCLUSIONS. For the first time, this work demonstrated the activity of NaClO2 in New World Leishmania. Additionally, it presented the pharmacotechnical potential of nanoformulations containing Anf-B for the treatment of ACL. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2019-08-19T13:13:00Z |
dc.date.available.fl_str_mv |
2019-08-19T13:13:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MAGALHAES, Carla Pires. Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose tegumentar. 2018. 101 f. Mestrado (Dissertação em Biotecnologia Biotecnologia em Saúde e Medicina Investigativa) - Instituto de Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2018. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/34870 |
identifier_str_mv |
MAGALHAES, Carla Pires. Desenvolvimento de nanoformulações de uso tópico contendo Anfotericina B e Clorito de sódio para Leishmaniose tegumentar. 2018. 101 f. Mestrado (Dissertação em Biotecnologia Biotecnologia em Saúde e Medicina Investigativa) - Instituto de Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, 2018. |
url |
https://www.arca.fiocruz.br/handle/icict/34870 |
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por |
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por |
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Instituto Gonçalo Moniz |
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Instituto Gonçalo Moniz |
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