The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells

• Published in: Pharmaceutics Vol. 14; no. 9; p. 1827
• Main Authors: Margari, Andrea, Monteduro, Anna Grazia, Rizzato, Silvia, Capobianco, Loredana, Crestini, Alessio, Rivabene, Roberto, Piscopo, Paola, D’Onofrio, Mara, Manzini, Valeria, Trapani, Giuseppe, Quarta, Alessandra, Maruccio, Giuseppe, Ventra, Carmelo, Lieto, Luigi, Trapani, Adriana
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30.08.2022; MDPI
• Subjects: 6-hydroxydopamine; Bioavailability; Biomedical materials; Chemical properties; citicoline; Cytidine diphosphate choline; Degeneration; Dopamine; Drug delivery systems; Drugs; Health aspects; Homogenization; Lipids; Nanoparticles; Nervous system; Neuroblastoma; Oxidative stress; Parkinson's disease; Pharmaceutical industry; Pharmaceutical research; SH-SY5Y dopaminergic cells; solid lipid nanoparticles; Vehicles; Italy; Germany
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14091827

(1) Backgrond: Considering the positive effects of citicoline (CIT) in the management of some neurodegenerative diseases, the aim of this work was to develop CIT-Loaded Solid Lipid Nanoparticles (CIT-SLNs) for enhancing the therapeutic use of CIT in parkinsonian syndrome; (2) Methods: CIT-SLNs were prepared by the melt homogenization method using the self-emulsifying lipid Gelucire® 50/13 as lipid matrix. Solid-state features on CIT-SLNs were obtained with FT-IR, thermal analysis (DSC) and X-ray powder diffraction (XRPD) studies. (3) Results: CIT-SLNs showed a mean diameter of 201 nm, −2.20 mV as zeta potential and a high percentage of entrapped CIT. DSC and XRPD analyses evidenced a greater amorphous state of CIT in CIT-SLNs. On confocal microscopy, fluorescent SLNs replacing unlabeled CIT-SLNs released the dye selectively in the cytoplasm. Biological evaluation showed that pre-treatment of SH-SY5Y dopaminergic cells with CIT-SLNs (50 µM) before the addition of 40 µM 6-hydroxydopamine (6-OHDA) to mimic Parkinson’s disease’s degenerative pathways counteracts the cytotoxic effects induced by the neurotoxin, increasing cell viability with the consistent maintenance of both nuclear and cell morphology. In contrast, pre-treatment with CIT 50 and 60 µM or plain SLNs for 2 h followed by 6-OHDA (40 µM) did not significantly influence cell viability. (4) Conclusions: These data suggest an enhanced protection exerted by CIT-SLNs with respect to free CIT and prompt further investigation of possible molecular mechanisms that underlie this difference.