Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders
Elvira De Giglio,
Udo Bakowsky,
Konrad Engelhardt,
Antonello Caponio,
Matteo La Pietra,
Stefania Cometa,
Stefano Castellani,
Lorenzo Guerra,
Giuseppe Fracchiolla,
Maria Luana Poeta,
Rosanna Mallamaci,
Rosa Angela Cardone,
Stefano Bellucci,
Adriana Trapani
Affiliations
Elvira De Giglio
Department of Chemistry, University of Bari “Aldo Moro”, 70125 Bari, Italy
Udo Bakowsky
Department of Pharmaceutics and Biopharmaceutics, Philipps University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Konrad Engelhardt
Department of Pharmaceutics and Biopharmaceutics, Philipps University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany
Antonello Caponio
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, Italy
Matteo La Pietra
Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, 00044 Frascati, Italy
Stefania Cometa
Jaber Innovation s.r.l., 00144 Rome, Italy
Stefano Castellani
Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, 70125 Bari, Italy
Lorenzo Guerra
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Giuseppe Fracchiolla
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, Italy
Maria Luana Poeta
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Rosanna Mallamaci
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Rosa Angela Cardone
Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
Stefano Bellucci
Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati, Via Enrico Fermi 54, 00044 Frascati, Italy
Adriana Trapani
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, Italy
(1) Background: DA-Gelucire® 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson’s disease (PD) treatment. To develop powders constituted by such SLNs for nasal administration, herein, two different agents, namely sucrose and methyl-β-cyclodextrin (Me-β-CD), were evaluated as cryoprotectants. (2) Methods: SLNs were prepared following the melt homogenization method, and their physicochemical features were investigated by Raman spectroscopy, Scanning Electron Microscopy (SEM), atomic force microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS). (3) Results: SLN size and zeta potential values changed according to the type of cryoprotectant and the morphological features investigated by SEM showed that the SLN samples after lyophilization appear as folded sheets with rough surfaces. On the other hand, the AFM visualization of the SLNs showed that their morphology consists of round-shaped particles before and after freeze-drying. XPS showed that when sucrose or Me-β-CD were not detected on the surface (because they were not allocated on the surface or completely absent in the formulation), then a DA surfacing was observed. In vitro release studies in Simulated Nasal Fluid evidenced that DA release, but not the GSE one, occurred from all the cryoprotected formulations. Finally, sucrose increased the physical stability of SLNs better than Me-β-CD, whereas RPMI 2650 cell viability was unaffected by SLN-sucrose and slightly reduced by SLN-Me-β-CD. (4) Conclusions: Sucrose can be considered a promising excipient, eliciting cryoprotection of the investigated SLNs, leading to a powder nasal pharmaceutical dosage form suitable to be handled by PD patients.
