Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders

Abstract

(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.

Dopamine- and Grape-Seed-Extract-Loaded Solid Lipid Nanoparticles: Interaction Studies between Particles and Differentiated SH-SY5Y Neuronal Cell Model of Parkinson’s Disease

“…The experimental design underlying the activities described in this article focused on evaluating two SLN formulations, namely DA-co-GSE-SLNs and GSE-ads-DA-SLNs, whose main physicochemical features are listed in Table 1. Both types of SLNs, whose size, zeta potential, and morphological external surface have been extensively characterized [31,32], were non-cytotoxic and endowed with cytoprotective effects against Rotenone activity (Figures 1 and 2).…”

“…In the context of a project aiming at brain delivery of new lipid nanocarriers by intranasal administration, we prepared two different types of in vitro formulations of SLNs combining the neurotransmitter DA and the natural antioxidant mixture Grape Seed Extract (GSE). We formulated SLNs in which both active principles were co-loaded with SLNs in which GSE was physically adsorbed onto preformed DA-SLNs [31,32], according to the working hypothesis that an antioxidant-based therapy might reduce ROS connected to PD along with providing a synergistic effect with the exogenous DA supply. Indeed, rather than exploiting the antioxidant effects arising from vitamin E [33,34], we selected polyphenols from GSE, mainly consisting of proanthocyanidins, to assess both their potential therapeutic and antioxidant effects.…”