Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Rosa, Marlon Erick Pereira
Orientador(a): Ricardo, Nágila Maria Pontes Silva
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/80840
Resumo: In Brazil, advances in science have allowed substances responsible for exhibiting antitumor activity to be isolated from native fauna and flora, such as anacardic acid (AA), extracted from the liquid from the shell of cashew nuts. However, this compound is hydrophobic, making it necessary to develop efficient vehicles for its administration in aqueous systems. In the literature, there are few studies that encapsulate AA in selective delivery systems for cancer treatment. Thus, the objective of the present work was to develop a microcapsule based on the polysaccharide sodium hyaluronate (HS), containing AA as the core, encapsulated from a nanoemulsion with licuri oil. For this, the nanoemulsion (NEAA) was obtained using the ultrasonication technique. The microcapsule (MCAA) was formed after adding NEAA to an aqueous solution of HS, followed by drying the resulting mixture using a spray dryer. The particle size of the aqueous redispersion of MCAA has a value of 292.1 ± 1.2 nm, suggesting that the polysaccharide encapsulation of the nanoemulsion was efficient and the zeta potential (-52.2 ± 1.2 mV) revealed an increase in stability parameters in relation to the nanoemulsion (- 29.7 ± 1.6 mV). MCAA presented an Encapsulation Efficiency value equal to 95.06 ± 1.22%. The Scanning Electron Microscopy revealed a spherical shape for the MCAA powder particles, with an average size of 3.7 ± 2.1 µm. The microcapsules achieved in vitro accumulated release of AA equal to 4.18 ± 0.75% at pH equal to 7.4, with a controlled release of AA in relation to the free active ingredient (27.33 ± 3.85%) and showed pH-responsive release, with a reduction in the percentage of AA at pH 6.8 (2.83 ± 0.39%) and pH 4.5 (0.18 ± 0.12%). In vivo tests did not produce acute toxicity in zebrafish or changes in locomotor activity after treatment with the formulation. The IC50 determined for the formulation presented values of 30.1 and 29.8 µg mL1 in HCT-116 and HL-60 tumor cells, respectively, and did not present a detectable IC50 in the concentration range tested for non-tumor L-929 cells. Thus, the AA encapsulation process through intermolecular interactions with licuri oil and later with HS allowed a reduction in toxicity in these cells compared to non-encapsulated AA (IC50 = 0.70 µg mL-1 in L-929), strongly suggesting a reduction in toxicity and possible side effects, being promising for future applications in cancer therapies.
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spelling Rosa, Marlon Erick PereiraRebouças, Louhana MoreiraRicardo, Nágila Maria Pontes Silva2025-05-13T18:12:26Z2025-05-13T18:12:26Z2025ROSA, Marlon Erick Pereira. Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal. 2025. 98 f. Dissertação (Mestrado em Química) - Universidade Federal do Ceará, Fortaleza, 2025.http://repositorio.ufc.br/handle/riufc/80840In Brazil, advances in science have allowed substances responsible for exhibiting antitumor activity to be isolated from native fauna and flora, such as anacardic acid (AA), extracted from the liquid from the shell of cashew nuts. However, this compound is hydrophobic, making it necessary to develop efficient vehicles for its administration in aqueous systems. In the literature, there are few studies that encapsulate AA in selective delivery systems for cancer treatment. Thus, the objective of the present work was to develop a microcapsule based on the polysaccharide sodium hyaluronate (HS), containing AA as the core, encapsulated from a nanoemulsion with licuri oil. For this, the nanoemulsion (NEAA) was obtained using the ultrasonication technique. The microcapsule (MCAA) was formed after adding NEAA to an aqueous solution of HS, followed by drying the resulting mixture using a spray dryer. The particle size of the aqueous redispersion of MCAA has a value of 292.1 ± 1.2 nm, suggesting that the polysaccharide encapsulation of the nanoemulsion was efficient and the zeta potential (-52.2 ± 1.2 mV) revealed an increase in stability parameters in relation to the nanoemulsion (- 29.7 ± 1.6 mV). MCAA presented an Encapsulation Efficiency value equal to 95.06 ± 1.22%. The Scanning Electron Microscopy revealed a spherical shape for the MCAA powder particles, with an average size of 3.7 ± 2.1 µm. The microcapsules achieved in vitro accumulated release of AA equal to 4.18 ± 0.75% at pH equal to 7.4, with a controlled release of AA in relation to the free active ingredient (27.33 ± 3.85%) and showed pH-responsive release, with a reduction in the percentage of AA at pH 6.8 (2.83 ± 0.39%) and pH 4.5 (0.18 ± 0.12%). In vivo tests did not produce acute toxicity in zebrafish or changes in locomotor activity after treatment with the formulation. The IC50 determined for the formulation presented values of 30.1 and 29.8 µg mL1 in HCT-116 and HL-60 tumor cells, respectively, and did not present a detectable IC50 in the concentration range tested for non-tumor L-929 cells. Thus, the AA encapsulation process through intermolecular interactions with licuri oil and later with HS allowed a reduction in toxicity in these cells compared to non-encapsulated AA (IC50 = 0.70 µg mL-1 in L-929), strongly suggesting a reduction in toxicity and possible side effects, being promising for future applications in cancer therapies.No Brasil, o avanço da ciência permitiu que substâncias responsáveis por apresentar atividade antitumoral fossem isoladas a partir da fauna e da flora nativas, como o ácido anacárdico (AA), extraído do líquido da casca da castanha do caju. No entanto, este composto é hidrofóbico, tornando necessário o desenvolvimento de veículos eficientes para a sua administração em sistemas aquosos. Na literatura, há poucos trabalhos que encapsulam AA em sistemas de entrega seletiva para o tratamento de câncer. Assim, o objetivo do presente trabalho foi desenvolver uma microcápsula à base do polissacarídeo hialuronato de sódio (HS), contendo como núcleo o AA, encapsulado a partir de nanoemulsão com óleo de licuri. Para isso, a nanoemulsão (NEAA) foi obtida através da técnica de ultrassonicação. A microcápsula (MCAA) foi formada após a adição de NEAA em uma solução aquosa de HS, seguido da secagem da mistura resultante com auxílio de um spray dryer. O tamanho de partícula da redispersão aquosa da MCAA possui valor de 292,1 ± 1,2 nm, sugerindo que a encapsulação polissacarídica da nanoemulsão foi eficiente e o potencial zeta (-52,2 ± 1,2 mV) revelou aumento nos parâmetros de estabilidade em relação à nanoemulsão (-29,7 ± 1,6 mV). A MCAA apresentou valor de Eficiência de Encapsulação igual a 95,06 ± 1,22%. A Microscopia Eletrônica de Varredura revelou formato esférico para as partículas da MCAA em pó, com tamanho médio igual a 3,7 ± 2,1 µm. As microcápsulas obtiveram liberação in vitro acumulada de AA igual a 4,18 ± 0,75% em pH igual a 7,4, com uma liberação controlada de AA em relação ao princípio ativo livre (27,33 ± 3,85%) e mostraram liberação responsiva ao pH, com redução do percentual de AA em pH 6,8 (2,83 ± 0,39%) e pH 4,5 (0,18 ± 0,12%). Os testes in vivo não produziram toxicidade aguda em zebrafish ou alterações na atividade locomotora após o tratamento com a formulação. A IC50 determinada para a formulação apresentou valores de 30,1 e 29,8 µg mL-1 em células tumorais HCT-116 e HL-60, respectivamente, e não apresentou IC50 detectável no intervalo de concentração testado para células não tumorais L-929. Assim, o processo de encapsulação de AA por meio de interações intermoleculares com o óleo de licuri e posteriormente com o HS permitiu reduzir a toxicidade nessas células em comparação ao AA não encapsulado (IC50 = 0,70 µg mL-1 em L-929), sugerindo fortemente redução da toxicidade e de possíveis efeitos colaterais, sendo promissora para futuras aplicações em terapias contra o câncer.Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretalSodium hyaluronate-based microcapsule for encapsulation of anacardic acid and potential application in the treatment of promyelocytic leukemia and colorectal cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMicrocápsulasÁcido anacárdicoHialuronato de sódioCâncerMicrocapsulesAnacardic acidSodium hyaluronateCancerCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttps://orcid.org/0009-0009-3098-514Xhttp://lattes.cnpq.br/2168464236066631https://orcid.org/0000-0003-1849-5403http://lattes.cnpq.br/6703037457253125https://orcid.org/0000-0001-7364-9474http://lattes.cnpq.br/64715430203323632025-05-13ORIGINAL2025_dis_meprosa.pdf2025_dis_meprosa.pdfapplication/pdf3385433http://repositorio.ufc.br/bitstream/riufc/80840/1/2025_dis_meprosa.pdfbe08c26b3e944ca8ea20e3aef31798a6MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/80840/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/808402025-05-13 15:12:28.28oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2025-05-13T18:12:28Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
dc.title.en.pt_BR.fl_str_mv Sodium hyaluronate-based microcapsule for encapsulation of anacardic acid and potential application in the treatment of promyelocytic leukemia and colorectal cancer
title Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
spellingShingle Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
Rosa, Marlon Erick Pereira
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
Microcápsulas
Ácido anacárdico
Hialuronato de sódio
Câncer
Microcapsules
Anacardic acid
Sodium hyaluronate
Cancer
title_short Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
title_full Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
title_fullStr Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
title_full_unstemmed Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
title_sort Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal
author Rosa, Marlon Erick Pereira
author_facet Rosa, Marlon Erick Pereira
author_role author
dc.contributor.co-advisor.none.fl_str_mv Rebouças, Louhana Moreira
dc.contributor.author.fl_str_mv Rosa, Marlon Erick Pereira
dc.contributor.advisor1.fl_str_mv Ricardo, Nágila Maria Pontes Silva
contributor_str_mv Ricardo, Nágila Maria Pontes Silva
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
topic CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
Microcápsulas
Ácido anacárdico
Hialuronato de sódio
Câncer
Microcapsules
Anacardic acid
Sodium hyaluronate
Cancer
dc.subject.ptbr.pt_BR.fl_str_mv Microcápsulas
Ácido anacárdico
Hialuronato de sódio
Câncer
dc.subject.en.pt_BR.fl_str_mv Microcapsules
Anacardic acid
Sodium hyaluronate
Cancer
description In Brazil, advances in science have allowed substances responsible for exhibiting antitumor activity to be isolated from native fauna and flora, such as anacardic acid (AA), extracted from the liquid from the shell of cashew nuts. However, this compound is hydrophobic, making it necessary to develop efficient vehicles for its administration in aqueous systems. In the literature, there are few studies that encapsulate AA in selective delivery systems for cancer treatment. Thus, the objective of the present work was to develop a microcapsule based on the polysaccharide sodium hyaluronate (HS), containing AA as the core, encapsulated from a nanoemulsion with licuri oil. For this, the nanoemulsion (NEAA) was obtained using the ultrasonication technique. The microcapsule (MCAA) was formed after adding NEAA to an aqueous solution of HS, followed by drying the resulting mixture using a spray dryer. The particle size of the aqueous redispersion of MCAA has a value of 292.1 ± 1.2 nm, suggesting that the polysaccharide encapsulation of the nanoemulsion was efficient and the zeta potential (-52.2 ± 1.2 mV) revealed an increase in stability parameters in relation to the nanoemulsion (- 29.7 ± 1.6 mV). MCAA presented an Encapsulation Efficiency value equal to 95.06 ± 1.22%. The Scanning Electron Microscopy revealed a spherical shape for the MCAA powder particles, with an average size of 3.7 ± 2.1 µm. The microcapsules achieved in vitro accumulated release of AA equal to 4.18 ± 0.75% at pH equal to 7.4, with a controlled release of AA in relation to the free active ingredient (27.33 ± 3.85%) and showed pH-responsive release, with a reduction in the percentage of AA at pH 6.8 (2.83 ± 0.39%) and pH 4.5 (0.18 ± 0.12%). In vivo tests did not produce acute toxicity in zebrafish or changes in locomotor activity after treatment with the formulation. The IC50 determined for the formulation presented values of 30.1 and 29.8 µg mL1 in HCT-116 and HL-60 tumor cells, respectively, and did not present a detectable IC50 in the concentration range tested for non-tumor L-929 cells. Thus, the AA encapsulation process through intermolecular interactions with licuri oil and later with HS allowed a reduction in toxicity in these cells compared to non-encapsulated AA (IC50 = 0.70 µg mL-1 in L-929), strongly suggesting a reduction in toxicity and possible side effects, being promising for future applications in cancer therapies.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-05-13T18:12:26Z
dc.date.available.fl_str_mv 2025-05-13T18:12:26Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv ROSA, Marlon Erick Pereira. Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal. 2025. 98 f. Dissertação (Mestrado em Química) - Universidade Federal do Ceará, Fortaleza, 2025.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/80840
identifier_str_mv ROSA, Marlon Erick Pereira. Microcápsula à base de hialuronato de sódio para encapsulação de ácido anacárdico e potencial aplicação em tratamento de leucemia promielocítica e câncer colorretal. 2025. 98 f. Dissertação (Mestrado em Química) - Universidade Federal do Ceará, Fortaleza, 2025.
url http://repositorio.ufc.br/handle/riufc/80840
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
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