Publicação
Permeability assay and inflammatory marker quantification of lactoferrin functionalized lipid nanoparticles intended for brain delivery
| Resumo: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a survival rate of 3 to 5 years from the onset of symptoms. ALS treatment is compromised by the existence of the blood-brain barrier (BBB), which restricts the access of promising biopharmaceutics to the brain, including riluzole, a drug commonly used to treat ALS. To circumvent the BBB and improve the drug brain targeting, nanosystems such as lipid nanoparticles can be employed. In this work, the permeation of nanostructured lipid carriers (NLC) loaded with riluzole and functionalized with a specific ligand – lactoferrin – was assessed in an in vitro BBB model (hCMEC/D3 cell line). Moreover, the effect of the NLC on the production and secretion of the pro-inflammatory cytokine human interleukin 1 alpha (IL-1a) by the cells was also quantified. The permeability studies across the hCMEC/D3 cell monolayers showed that free riluzole penetrated the BBB more than the riluzole-loaded NLC, which was also consistent with the results from the ELISA kit, with the free drug eliciting a higher IL-1a production. Despite these findings, the developed nanocarriers possessed good biocompatibility and stability, and could, therefore, be considered suitable for brain applications. |
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| Autores principais: | Teixeira, Maria Inês |
| Outros Autores: | Lopes, Carla Martins; Reguengo, Henrique; Oliveira, José Carlos; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C. |
| Assunto: | Blood-brain barrier (BBB) Brain delivery Neurodegeneration Amyotrophic lateral sclerosis (ALS) Functionalized lipid nanoparticles Nanostructured lipid carriers (NLC) Riluzole Lactoferrin |
| Ano: | 2022 |
| País: | Portugal |
| Tipo de documento: | documento de conferência |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade Fernando Pessoa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da Fernando Pessoa |
| Resumo: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a survival rate of 3 to 5 years from the onset of symptoms. ALS treatment is compromised by the existence of the blood-brain barrier (BBB), which restricts the access of promising biopharmaceutics to the brain, including riluzole, a drug commonly used to treat ALS. To circumvent the BBB and improve the drug brain targeting, nanosystems such as lipid nanoparticles can be employed. In this work, the permeation of nanostructured lipid carriers (NLC) loaded with riluzole and functionalized with a specific ligand – lactoferrin – was assessed in an in vitro BBB model (hCMEC/D3 cell line). Moreover, the effect of the NLC on the production and secretion of the pro-inflammatory cytokine human interleukin 1 alpha (IL-1a) by the cells was also quantified. The permeability studies across the hCMEC/D3 cell monolayers showed that free riluzole penetrated the BBB more than the riluzole-loaded NLC, which was also consistent with the results from the ELISA kit, with the free drug eliciting a higher IL-1a production. Despite these findings, the developed nanocarriers possessed good biocompatibility and stability, and could, therefore, be considered suitable for brain applications. |
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