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- Formulation, characterization, and cytotoxicity evaluation of lactoferrin functionalized lipid nanoparticles for riluzole delivery to the brainPublication . Teixeira, Maria Inês; Lopes, Carla Martins; Gonçalves, Hugo; Catita, José; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C.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.
- Riluzole-loaded lipid nanoparticles for brain delivery: preparation, optimization and characterizationPublication . Teixeira, Maria Inês; Lopes, Carla Martins; Gonçalves, Hugo; Catita, José; Silva, Ana Margarida; Rodrigues, Francisca; Amaral, Maria Helena; Costa, Paulo C.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with a median survival of only 2 to 4 years. Riluzole, a drug commonly used in the management of ALS, has a low aqueous solubility and limited bioavailability. ALS treatment is also hindered by the presence of the blood–brain barrier (BBB) that preserves the delicate homeostasis of the cerebral milieu, isolating it and making brain drug delivery exceptionally hard. To overcome these issues, the use of lipid nanocarriers, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), is a promising strategy. In this study, SLN and NLC were prepared and optimized to facilitate riluzole uptake into the brain for ALS therapy. The lipid nanoparticles were characterized through different techniques, with respect to their physicochemical properties (size, zeta potential (ZP), polydispersity index (PDI)), as well as encapsulation efficiency, morphology, stability, in vitro release, crystallinity, and biocompatibility. Riluzole-loaded nanocarriers exhibited characteristics suitable for brain delivery, including mean diameters between 147.2 and 203.1 nm, low PDI (<0.3), and negative ZP between − 22.5 and − 27.5 mV. Additionally, they were physically stable over 3 months under storage conditions (5 ℃ and 25 ℃), promoting a slow and sustained release of the drug, which was shown to be inside the core of the lipid matrix. Cytotoxicity assays demonstrated that both SLN and NLC did not significantly affect the viability of an hCMEC/D3 cell monolayer at a riluzole concentration up to 10 μM. The results suggest that the developed nanocarriers could be a viable platform to target riluzole to the central nervous system (CNS). Nevertheless, further in vitro and in vivo studies are needed to validate their therapeutic efficacy and safety.