The Encapsulation of Citicoline within Solid Lipid Nanoparticles Enhances Its Capability to Counteract the 6-Hydroxydopamine-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells
Andrea Margari,
Anna Grazia Monteduro,
Silvia Rizzato,
Loredana Capobianco,
Alessio Crestini,
Roberto Rivabene,
Paola Piscopo,
Mara D’Onofrio,
Valeria Manzini,
Giuseppe Trapani,
Alessandra Quarta,
Giuseppe Maruccio,
Carmelo Ventra,
Luigi Lieto,
Adriana Trapani
Affiliations
Andrea Margari
Omnics Research Group, Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento and INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, Italy
Anna Grazia Monteduro
Omnics Research Group, Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento and INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, Italy
Silvia Rizzato
Omnics Research Group, Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento and INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, Italy
Loredana Capobianco
Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
Alessio Crestini
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 00161 Rome, Italy
Roberto Rivabene
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 00161 Rome, Italy
Paola Piscopo
Department of Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 00161 Rome, Italy
Mara D’Onofrio
European Brain Research Institute (EBRI) “Rita Levi-Montalcini”, Viale Regina Elena, 00161 Rome, Italy
Valeria Manzini
European Brain Research Institute (EBRI) “Rita Levi-Montalcini”, Viale Regina Elena, 00161 Rome, Italy
Giuseppe Trapani
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona, 70125 Bari, Italy
Alessandra Quarta
CNR-NANOTEC Institute of Nanotechnology, Via Monteroni, 73100 Lecce, Italy
Giuseppe Maruccio
Omnics Research Group, Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento and INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, Italy
Carmelo Ventra
Esseti Farmaceutici, Via Cavalli di Bronzo, 39-46, San Giorgio a Cremano, 80046 Naples, Italy
Luigi Lieto
Esseti Farmaceutici, Via Cavalli di Bronzo, 39-46, San Giorgio a Cremano, 80046 Naples, Italy
Adriana Trapani
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona, 70125 Bari, Italy
(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.
