Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10400.6/11204 |
Resumo: | Breast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer. |
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Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer modelsSolid lipid nanoparticles (SLN)MitoxantroneBox-Behnken designChemotherapyBreast cancerTumor spheroidsBreast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer.ElsevieruBibliorumGranja, AndreiaSousa, Rita LimaAlves, CátiaDiogo, Duarte de MeloPinheiro, MarinaSousa, Célia T.Correia, I.J.Reis, Salette2023-08-29T00:30:23Z2021-08-212021-08-21T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.6/11204eng10.1016/j.ijpharm.2021.121044info: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:RCAAP2023-12-15T09:53:33Zoai:ubibliorum.ubi.pt:10400.6/11204Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:51:03.303220Repositório 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 |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
title |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
spellingShingle |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models Granja, Andreia Solid lipid nanoparticles (SLN) Mitoxantrone Box-Behnken design Chemotherapy Breast cancer Tumor spheroids |
title_short |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
title_full |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
title_fullStr |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
title_full_unstemmed |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
title_sort |
Mitoxantrone-loaded lipid nanoparticles for breast cancer therapy – quality-by-design approach and efficacy assessment in 2D and 3D in vitro cancer models |
author |
Granja, Andreia |
author_facet |
Granja, Andreia Sousa, Rita Lima Alves, Cátia Diogo, Duarte de Melo Pinheiro, Marina Sousa, Célia T. Correia, I.J. Reis, Salette |
author_role |
author |
author2 |
Sousa, Rita Lima Alves, Cátia Diogo, Duarte de Melo Pinheiro, Marina Sousa, Célia T. Correia, I.J. Reis, Salette |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
uBibliorum |
dc.contributor.author.fl_str_mv |
Granja, Andreia Sousa, Rita Lima Alves, Cátia Diogo, Duarte de Melo Pinheiro, Marina Sousa, Célia T. Correia, I.J. Reis, Salette |
dc.subject.por.fl_str_mv |
Solid lipid nanoparticles (SLN) Mitoxantrone Box-Behnken design Chemotherapy Breast cancer Tumor spheroids |
topic |
Solid lipid nanoparticles (SLN) Mitoxantrone Box-Behnken design Chemotherapy Breast cancer Tumor spheroids |
description |
Breast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-08-21 2021-08-21T00:00:00Z 2023-08-29T00:30:23Z |
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/10400.6/11204 |
url |
http://hdl.handle.net/10400.6/11204 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1016/j.ijpharm.2021.121044 |
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 |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136399911288832 |