Dopamine and Citicoline-Co-Loaded Solid Lipid Nanoparticles as Multifunctional Nanomedicines for Parkinson’s Disease Treatment by Intranasal Administration
Stefano Castellani,
Giorgia Natalia Iaconisi,
Francesca Tripaldi,
Vito Porcelli,
Adriana Trapani,
Eugenia Messina,
Lorenzo Guerra,
Cinzia Di Franco,
Giuseppe Maruccio,
Anna Grazia Monteduro,
Filomena Corbo,
Sante Di Gioia,
Giuseppe Trapani,
Massimo Conese
Affiliations
Stefano Castellani
Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70125 Bari, Italy
Giorgia Natalia Iaconisi
Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy
Francesca Tripaldi
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy
Vito Porcelli
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Adriana Trapani
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy
Eugenia Messina
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Lorenzo Guerra
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Cinzia Di Franco
CNR-IFN Bari, Bari Via Amendola 173, 70126 Bari, 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
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
Filomena Corbo
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy
Sante Di Gioia
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Giuseppe Trapani
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy
Massimo Conese
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
This work aimed to evaluate the potential of the nanosystems constituted by dopamine (DA) and the antioxidant Citicoline (CIT) co-loaded in solid lipid nanoparticles (SLNs) for intranasal administration in the treatment of Parkinson disease (PD). Such nanosystems, denoted as DA-CIT-SLNs, were designed according to the concept of multifunctional nanomedicine where multiple biological roles are combined into a single nanocarrier and prepared by the melt emulsification method employing the self-emulsifying Gelucire® 50/13 as lipid matrix. The resulting DA-CIT-SLNs were characterized regarding particle size, surface charge, encapsulation efficiency, morphology, and physical stability. Differential scanning calorimetry, FT-IR, and X ray diffraction studies were carried out to gain information on solid-state features, and in vitro release tests in simulated nasal fluid (SNF) were performed. Monitoring the particle size at two temperatures (4 °C and 37 °C), the size enlargement observed over the time at 37 °C was lower than that observed at 4 °C, even though at higher temperature, color changes occurred, indicative of possible neurotransmitter decomposition. Solid-state studies indicated a reduction in the crystallinity when DA and CIT are co-encapsulated in DA-CIT-SLNs. Interestingly, in vitro release studies in SNF indicated a sustained release of DA. Furthermore, DA-CIT SLNs displayed high cytocompatibility with both human nasal RPMI 2650 and neuronal SH-SY5Y cells. Furthermore, OxyBlot assay demonstrated considerable potential to assess the protective effect of antioxidant agents against oxidative cellular damage. Thus, such protective effect was shown by DA-CIT-SLNs, which constitute a promising formulation for PD application.
