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Advisor(s)
Abstract(s)
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.
Description
Keywords
Blood-brain barrier (BBB) Brain delivery Neurodegeneration Amyotrophic lateral sclerosis (ALS) Functionalized lipid nanoparticles Nanostructured lipid carriers (NLC) Riluzole Lactoferrin
Citation
Teixeira, M.I.; Lopes, C.M.; Reguengo, H.; Oliveira, J.C.; Silva, A.M.; Rodrigues, F.; Amaral, M.H. and Costa, P.C. (2022). Permeability assay and inflammatory marker quantification of lactoferrin functionalized lipid nanoparticles intended for brain delivery. Proceedings of the Nanotech International Conference (Nanotech France 2022), 15th – 17th June, Paris, France.