Claudia Machado
| Nanocarrier-Based Co-Delivery of Edaravone and Riluzole for Improved ALS Treatment Strategies |
| Cláudia S. Machado1, Ana Rita Alfenim1, Joana Moreira1, Brandon Aguiar2, Miguel Pinto1 Fernanda Borges2 and Carlos Fernandes1 1 RISE-Health, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal. 2 RISE-Health, Faculty of Sciences, University of Porto, Rua do Campo Alegre s/n, 4169-007, Porto, Portugal. |
| Abstract Amyotrophic lateral sclerosis (ALS) is known to be fatal and the most common degenerative disease of the motoneuron system, possibly involving various genetic and molecular pathways, that still lack effective treatment. Edaravone (Edv), a free radical scavenger, and Riluzole (Ril), a glutamate release inhibitor, are two approved drugs for ALS therapy. However, these are limited as they can only target one mechanism and present biocompatibility issues [1]. Nanotechnology-based drug delivery systems arise as a powerful tool for enhancing therapeutic bioavailability by inferring drug stability and targeting the desired site [2]. Furthermore, the combination of drugs that aim different pathways in the same nanocarrier brings an advantage over the conventional methodologies as a synergy of different drugs can be achieved. In this work, we encapsulated both Edv and Ril in different drug delivery systems using polymeric, lipidic or a mixture of both lipid and polymer core. For that, polylactic-co-glycolic acid (PLGA) nanoparticles, nanostructured lipid carriers (NLCs) and lipid-polymer hybrid nanoparticles (LPHNPs) were developed and functionalized with PEG or Vitamin E (TPGS) in order to verify the effect on the stability and interaction with cellular models. Drug delivery systems were analyzed by Dynamic and Electrophoretic Light Scattering to verify their storage stability. The interaction with mucus protein as well as the behavior of the nanocarriers in different pH media was also evaluated. The pharmacological profile of the most promising nanoformulation was evaluated in an in vitro cellular study using mouse motor neuron-Like (NSC-34) hybrid cell line |
| References [1] Xu, X., et al., A perspective on therapies for amyotrophic lateral sclerosis: can disease progression be curbed? Transl Neurodegener, 2021. 10(1): p. 29. https://doi.org/10.1186/s40035-021-00250-5 [2] Nabizadeh, F., Biomaterials in The Treatment of Amyotrophic Lateral Sclerosis. Neurology Letters, 2022. 1(1): p. 12-16. https://doi.org/10.52547/nl.1.1.12 Funding This work was funded by FEDER funds through national funds by FCT – Foundation for Science and Technology under research grants 2023.13291.PEX and under the project RISE-Health – UID/06397/2025. This work was also supported by the project IMPULSE (Funding programme: Horizon Europe; Grant agreement number: 101132028). This work was also supported by FCT by project reference 2021. 04016.CEECIND/CP1655/CT000(DOI: 10.54499/2021.04016.CEECIND/CP1655/CT0004). M.P. (101132028), J.M. (2023.13291.PEX/201569), B.A. (2020.08731.BD), A.R.A. (2023.01250.BD), C.S.M. (2024.00809.BD) grants are also supported by FCT. C.F. thanks the FCT for the financial support of his work contract through the Scientific Employment Stimulus—Individual Call (2021. 04016.CEECIND/CP1655/CT0004). |