Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/10284/10656 |
Resumo: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain. |
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Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brainBlood–brain barrier (BBB)Brain deliveryNeurodegenerative diseasesAmyotrophic lateral sclerosis (ALS)Lipid nanoparticleNanostructured lipid carriers (NLC)RiluzoleLactoferrinLactoferrin receptorsDrug targetingAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain.MDPIRepositório Institucional da Universidade Fernando PessoaTeixeira, Maria InêsLopes, Carla MartinsGonçalves, HugoCatita, JoséSilva, Ana MargaridaRodrigues, FranciscaAmaral, Maria HelenaCosta, Paulo C.2022-01-19T12:40:54Z2022-01-132022-01-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/10656engTeixeira, M.I.; Lopes, C.M.; Gonçalves, H.; Catita, J.; Silva, A.M.; Rodrigues, F.; Amaral, M.H.; Costa, P.C. Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain. Pharmaceutics 2022, 14, 185. https://doi.org/10.3390/ pharmaceutics140101851999-492310.3390/pharmaceutics14010185info: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:RCAAP2024-02-06T02:01:20Zoai:bdigital.ufp.pt:10284/10656Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:47:25.187152Repositório 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 |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
title |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
spellingShingle |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain Teixeira, Maria Inês Blood–brain barrier (BBB) Brain delivery Neurodegenerative diseases Amyotrophic lateral sclerosis (ALS) Lipid nanoparticle Nanostructured lipid carriers (NLC) Riluzole Lactoferrin Lactoferrin receptors Drug targeting |
title_short |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
title_full |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
title_fullStr |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
title_full_unstemmed |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
title_sort |
Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brain |
author |
Teixeira, Maria Inês |
author_facet |
Teixeira, Maria Inês Lopes, Carla Martins Gonçalves, Hugo Catita, José Silva, Ana Margarida Rodrigues, Francisca Amaral, Maria Helena Costa, Paulo C. |
author_role |
author |
author2 |
Lopes, Carla Martins Gonçalves, Hugo Catita, José Silva, Ana Margarida Rodrigues, Francisca Amaral, Maria Helena Costa, Paulo C. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Teixeira, Maria Inês Lopes, Carla Martins Gonçalves, Hugo Catita, José Silva, Ana Margarida Rodrigues, Francisca Amaral, Maria Helena Costa, Paulo C. |
dc.subject.por.fl_str_mv |
Blood–brain barrier (BBB) Brain delivery Neurodegenerative diseases Amyotrophic lateral sclerosis (ALS) Lipid nanoparticle Nanostructured lipid carriers (NLC) Riluzole Lactoferrin Lactoferrin receptors Drug targeting |
topic |
Blood–brain barrier (BBB) Brain delivery Neurodegenerative diseases Amyotrophic lateral sclerosis (ALS) Lipid nanoparticle Nanostructured lipid carriers (NLC) Riluzole Lactoferrin Lactoferrin receptors Drug targeting |
description |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-19T12:40:54Z 2022-01-13 2022-01-13T00:00:00Z |
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/10284/10656 |
url |
http://hdl.handle.net/10284/10656 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Teixeira, M.I.; Lopes, C.M.; Gonçalves, H.; Catita, J.; Silva, A.M.; Rodrigues, F.; Amaral, M.H.; Costa, P.C. Formulation, Characterization, and Cytotoxicity Evaluation of Lactoferrin Functionalized Lipid Nanoparticles for Riluzole Delivery to the Brain. Pharmaceutics 2022, 14, 185. https://doi.org/10.3390/ pharmaceutics14010185 1999-4923 10.3390/pharmaceutics14010185 |
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 |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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