Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMT |
Texto Completo: | http://ri.ufmt.br/handle/1/4468 |
Resumo: | Central nervous system tumors are among the ten tumors which present the highest risk of new cases in Brazil. Considering these tumors, glioblastoma stands out as it has a high mortality rate, with an estimated survival time between 6 and 15 months. There is increasing evidence that artemisinin derivatives, such as artemether, represent a new class of semi-synthetic sesquiterpene lactones with antitumor activity, possibly through inducing the intracellular formation of reactive oxygen species and apoptosis. However, artemether presents characteristics that limit its pharmacological action, such as low bioavailability, low water solubility, and physicochemical instability. Nanoencapsulation is an alternative to minimize these effects and potentiate the action of the drug, besides promoting the passage through the blood-brain barrier. In this scenario, pequi oil (Caryocar brasiliense Cambess) represents a promising candidate for use as a structural component in nanosystems, as it promotes drug solubilization and is also known for its ability to reduce adverse effects of chemotherapy on normal cells. Considering the high lethality of glioblastomas, the ineffectiveness of current therapies and the prospect of using artemether for this purpose, the objective of this work was to develop polymeric lipid core nanocapsules containing pequi oil (Caryocar brasiliense Cambess) as a structuring agent for artemether nanocarrying and evaluation of its effect on human glioblastoma cells (U-87 MG). Nanocapsule suspensions were developed by interfacial deposition preformed polymer and characterized by determining the mean particle diameter, zeta potential, and pH. Cytotoxicity was assessed by mitochondrial viability (MTT) and cell density and proliferation by sulforhodamine B staining. Total antioxidant capacity and antioxidant enzymes activity were determined to evaluate the effect of free and nanostructured artemether on the redox state of the cells. The nanosystems presented a mean size of 200 nm, low polydispersity index, zeta potential close to -10 mV, and slightly acidic pH. The free artemether reduced cell viability after 24h of treatment and proliferation after 48h of treatment at concentrations equal to or above 40 µg.mL-1 (134 µM). The nanoencapsulated artemether reduced these parameters after 24h of treatment, at the concentration of 1.25 µg.mL-1 . When evaluating the effect of nanostructured artemether (1.25 µg.mL-1 ) on the antioxidant enzymes, there was an increase in the activity of SOD and decrease in GR activity in U-87 MG cells. However, this effect was not observed when the cells were treated with free artemether at the same concentration. These findings are consistent with the proposed mechanism for the action of artemether, which is the induction of oxidative stress, and indicate potentiation of its antitumor action. From the data presented, we conclude that pequi oil (Caryocar brasiliense Cambess) presents appropriate characteristics to be used as a structuring agent in the development of nanocapsules containing artemether, as well as other chemotherapeutic agents, and we open the prospect for further studies on this nanosystem. |
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Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitroNanocápsulas poliméricas de núcleo lipídicoCaryocar brasiliense CambessArtemeterGlioblastoma humanoCNPQ::CIENCIAS DA SAUDE::MEDICINAPolymeric lipid-core nanocapsulesCaryocar brasiliense cambess artemetherHuman glioblastomaCentral nervous system tumors are among the ten tumors which present the highest risk of new cases in Brazil. Considering these tumors, glioblastoma stands out as it has a high mortality rate, with an estimated survival time between 6 and 15 months. There is increasing evidence that artemisinin derivatives, such as artemether, represent a new class of semi-synthetic sesquiterpene lactones with antitumor activity, possibly through inducing the intracellular formation of reactive oxygen species and apoptosis. However, artemether presents characteristics that limit its pharmacological action, such as low bioavailability, low water solubility, and physicochemical instability. Nanoencapsulation is an alternative to minimize these effects and potentiate the action of the drug, besides promoting the passage through the blood-brain barrier. In this scenario, pequi oil (Caryocar brasiliense Cambess) represents a promising candidate for use as a structural component in nanosystems, as it promotes drug solubilization and is also known for its ability to reduce adverse effects of chemotherapy on normal cells. Considering the high lethality of glioblastomas, the ineffectiveness of current therapies and the prospect of using artemether for this purpose, the objective of this work was to develop polymeric lipid core nanocapsules containing pequi oil (Caryocar brasiliense Cambess) as a structuring agent for artemether nanocarrying and evaluation of its effect on human glioblastoma cells (U-87 MG). Nanocapsule suspensions were developed by interfacial deposition preformed polymer and characterized by determining the mean particle diameter, zeta potential, and pH. Cytotoxicity was assessed by mitochondrial viability (MTT) and cell density and proliferation by sulforhodamine B staining. Total antioxidant capacity and antioxidant enzymes activity were determined to evaluate the effect of free and nanostructured artemether on the redox state of the cells. The nanosystems presented a mean size of 200 nm, low polydispersity index, zeta potential close to -10 mV, and slightly acidic pH. The free artemether reduced cell viability after 24h of treatment and proliferation after 48h of treatment at concentrations equal to or above 40 µg.mL-1 (134 µM). The nanoencapsulated artemether reduced these parameters after 24h of treatment, at the concentration of 1.25 µg.mL-1 . When evaluating the effect of nanostructured artemether (1.25 µg.mL-1 ) on the antioxidant enzymes, there was an increase in the activity of SOD and decrease in GR activity in U-87 MG cells. However, this effect was not observed when the cells were treated with free artemether at the same concentration. These findings are consistent with the proposed mechanism for the action of artemether, which is the induction of oxidative stress, and indicate potentiation of its antitumor action. From the data presented, we conclude that pequi oil (Caryocar brasiliense Cambess) presents appropriate characteristics to be used as a structuring agent in the development of nanocapsules containing artemether, as well as other chemotherapeutic agents, and we open the prospect for further studies on this nanosystem.CAPESTumores do sistema nervoso central estão entre os dez tumores que apresentam maior risco de casos novos no Brasil. Dentre eles, destaca-se o glioblastoma, por este apresentar maior taxa de mortalidade com tempo de sobrevida estimado entre 6 a 15 meses. Há evidências crescentes de que os derivados da artemisinina, como o artemeter, representam uma nova classe de lactonas sesquiterpênicas semissintéticas com atividade antitumoral, possivelmente por induzir a formação intracelular de espécies reativas de oxigênio e apoptose. No entanto, o artemeter apresenta características que limitam sua ação farmacológica, como baixa biodisponibilidade, baixa solubilidade em água e instabilidade físico-química. A nanoencapsulação é uma alternativa para minimizar estes efeitos e potencializar a ação do fármaco, além de promover a passagem através da barreira hematoencefálica. Neste cenário, o óleo de pequi (Caryocar brasiliense Cambess) torna-se um promissor candidato para a utilização como componente estrutural em nanossistemas, pois além de favorecer a solubilização do fármaco, também é conhecido por sua capacidade de reduzir efeitos adversos de quimioterápicos em células normais. Considerando a elevada letalidade dos glioblastomas, a ineficácia das terapias vigentes e a perspectiva de uso do artemeter para esta finalidade, o objetivo deste trabalho foi desenvolver nanocápsulas poliméricas de núcleo lipídico, contendo óleo de pequi (Caryocar brasiliense Cambess) como agente estruturante, para o nanocarreamento do artemeter e avaliação do seu efeito em células de glioblastoma humano (U-87 MG). As suspensões de nanocápsulas foram desenvolvidas por deposição interfacial do polímero pré-formado e caracterizadas determinando-se o diâmetro médio da partícula, potencial zeta e pH. A citotoxicidade foi avaliada pela viabilidade mitocondrial (MTT) e a densidade e proliferação celular por coloração com sulforrodamina B. A capacidade antioxidante total e a atividade das enzimas antioxidantes foram determinadas visando avaliar o efeito do artemeter livre e nanoestruturado sobre o estado redox das células. Os nanossistemas apresentaram tamanho médio de 200 nm, baixo índice de polidispersão, potencial zeta próximo a - 10 mV e pH levemente ácido. O artemeter livre reduziu a viabilidade celular após 24h de tratamento e a proliferação após 48h de tratamento, em concentrações iguais ou acima de 40 µg.mL-1 (134 µM). Já o artemeter nanoencapsulado reduziu esses parâmetros após 24h de tratamento, na concentração de 1,25 µg.mL-1 . Ao avaliar o efeito do artemeter nanoestruturado (1,25 µg.mL-1 ) sobre as enzimas antioxidantes, observou-se aumento na atividade da SOD e redução na atividade da GR, nas células U-87 MG. Entretanto, esse efeito não foi observado quando as células foram tratadas com artemeter livre na mesma concentração. Estes achados condizem com o mecanismo proposto para a ação do artemeter, que é a indução do estresse oxidativo, além de indicarem a potencialização da ação antitumoral do mesmo. Através dos dados apresentados, concluímos que o óleo de pequi (Caryocar brasiliense Cambess) apresenta características adequadas para ser utilizado como agente estruturante no desenvolvimento de nanocápsulas contendo o artemeter, bem como outros quimioterápicos, e abrimos a perspectiva de estudos mais aprofundados sobre esse nanossistema.Universidade Federal de Mato GrossoBrasilFaculdade de Medicina (FM)UFMT CUC - CuiabáPrograma de Pós-Graduação em Ciências da SaúdeAndrade, Cláudia Marlise BalbinottiFerrarini, Stela Reginahttp://lattes.cnpq.br/9781791623443251http://lattes.cnpq.br/7129682665041036Andrade, Cláudia Marlise Balbinotti899.065.600-10http://lattes.cnpq.br/7129682665041036Gai, Bibiana Mozzaquatro006.882.340-11http://lattes.cnpq.br/4903325870217874899.065.600-10000.848.650-67Bernardi, Andressa989.351.350-20http://lattes.cnpq.br/4161702873261271Pires, Jader2023-07-12T14:26:59Z2019-08-302023-07-12T14:26:59Z2019-05-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPIRES, Jader. Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro. 2019. 75 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2019.http://ri.ufmt.br/handle/1/4468porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMTinstname:Universidade Federal de Mato Grosso (UFMT)instacron:UFMT2023-07-20T07:05:28Zoai:localhost:1/4468Repositório InstitucionalPUBhttp://ri.ufmt.br/oai/requestjordanbiblio@gmail.comopendoar:2023-07-20T07:05:28Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT)false |
dc.title.none.fl_str_mv |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
title |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
spellingShingle |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro Pires, Jader Nanocápsulas poliméricas de núcleo lipídico Caryocar brasiliense Cambess Artemeter Glioblastoma humano CNPQ::CIENCIAS DA SAUDE::MEDICINA Polymeric lipid-core nanocapsules Caryocar brasiliense cambess artemether Human glioblastoma |
title_short |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
title_full |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
title_fullStr |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
title_full_unstemmed |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
title_sort |
Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro |
author |
Pires, Jader |
author_facet |
Pires, Jader |
author_role |
author |
dc.contributor.none.fl_str_mv |
Andrade, Cláudia Marlise Balbinotti Ferrarini, Stela Regina http://lattes.cnpq.br/9781791623443251 http://lattes.cnpq.br/7129682665041036 Andrade, Cláudia Marlise Balbinotti 899.065.600-10 http://lattes.cnpq.br/7129682665041036 Gai, Bibiana Mozzaquatro 006.882.340-11 http://lattes.cnpq.br/4903325870217874 899.065.600-10 000.848.650-67 Bernardi, Andressa 989.351.350-20 http://lattes.cnpq.br/4161702873261271 |
dc.contributor.author.fl_str_mv |
Pires, Jader |
dc.subject.por.fl_str_mv |
Nanocápsulas poliméricas de núcleo lipídico Caryocar brasiliense Cambess Artemeter Glioblastoma humano CNPQ::CIENCIAS DA SAUDE::MEDICINA Polymeric lipid-core nanocapsules Caryocar brasiliense cambess artemether Human glioblastoma |
topic |
Nanocápsulas poliméricas de núcleo lipídico Caryocar brasiliense Cambess Artemeter Glioblastoma humano CNPQ::CIENCIAS DA SAUDE::MEDICINA Polymeric lipid-core nanocapsules Caryocar brasiliense cambess artemether Human glioblastoma |
description |
Central nervous system tumors are among the ten tumors which present the highest risk of new cases in Brazil. Considering these tumors, glioblastoma stands out as it has a high mortality rate, with an estimated survival time between 6 and 15 months. There is increasing evidence that artemisinin derivatives, such as artemether, represent a new class of semi-synthetic sesquiterpene lactones with antitumor activity, possibly through inducing the intracellular formation of reactive oxygen species and apoptosis. However, artemether presents characteristics that limit its pharmacological action, such as low bioavailability, low water solubility, and physicochemical instability. Nanoencapsulation is an alternative to minimize these effects and potentiate the action of the drug, besides promoting the passage through the blood-brain barrier. In this scenario, pequi oil (Caryocar brasiliense Cambess) represents a promising candidate for use as a structural component in nanosystems, as it promotes drug solubilization and is also known for its ability to reduce adverse effects of chemotherapy on normal cells. Considering the high lethality of glioblastomas, the ineffectiveness of current therapies and the prospect of using artemether for this purpose, the objective of this work was to develop polymeric lipid core nanocapsules containing pequi oil (Caryocar brasiliense Cambess) as a structuring agent for artemether nanocarrying and evaluation of its effect on human glioblastoma cells (U-87 MG). Nanocapsule suspensions were developed by interfacial deposition preformed polymer and characterized by determining the mean particle diameter, zeta potential, and pH. Cytotoxicity was assessed by mitochondrial viability (MTT) and cell density and proliferation by sulforhodamine B staining. Total antioxidant capacity and antioxidant enzymes activity were determined to evaluate the effect of free and nanostructured artemether on the redox state of the cells. The nanosystems presented a mean size of 200 nm, low polydispersity index, zeta potential close to -10 mV, and slightly acidic pH. The free artemether reduced cell viability after 24h of treatment and proliferation after 48h of treatment at concentrations equal to or above 40 µg.mL-1 (134 µM). The nanoencapsulated artemether reduced these parameters after 24h of treatment, at the concentration of 1.25 µg.mL-1 . When evaluating the effect of nanostructured artemether (1.25 µg.mL-1 ) on the antioxidant enzymes, there was an increase in the activity of SOD and decrease in GR activity in U-87 MG cells. However, this effect was not observed when the cells were treated with free artemether at the same concentration. These findings are consistent with the proposed mechanism for the action of artemether, which is the induction of oxidative stress, and indicate potentiation of its antitumor action. From the data presented, we conclude that pequi oil (Caryocar brasiliense Cambess) presents appropriate characteristics to be used as a structuring agent in the development of nanocapsules containing artemether, as well as other chemotherapeutic agents, and we open the prospect for further studies on this nanosystem. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-08-30 2019-05-31 2023-07-12T14:26:59Z 2023-07-12T14:26:59Z |
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.uri.fl_str_mv |
PIRES, Jader. Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro. 2019. 75 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2019. http://ri.ufmt.br/handle/1/4468 |
identifier_str_mv |
PIRES, Jader. Desenvolvimento de nanossistemas com óleo de pequi (Caryocar brasiliense Cambess) para nanoestruturação do artemeter e avaliação do potencial antitumoral in vitro. 2019. 75 f. Dissertação (Mestrado em Ciências da Saúde) - Universidade Federal de Mato Grosso, Faculdade de Medicina, Cuiabá, 2019. |
url |
http://ri.ufmt.br/handle/1/4468 |
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por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Mato Grosso Brasil Faculdade de Medicina (FM) UFMT CUC - Cuiabá Programa de Pós-Graduação em Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Mato Grosso Brasil Faculdade de Medicina (FM) UFMT CUC - Cuiabá Programa de Pós-Graduação em Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMT instname:Universidade Federal de Mato Grosso (UFMT) instacron:UFMT |
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Universidade Federal de Mato Grosso (UFMT) |
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UFMT |
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UFMT |
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Repositório Institucional da UFMT |
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Repositório Institucional da UFMT |
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Repositório Institucional da UFMT - Universidade Federal de Mato Grosso (UFMT) |
repository.mail.fl_str_mv |
jordanbiblio@gmail.com |
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1800846280748957696 |