Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles

Abstract

Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.

Solid Lipid Nanoparticles Administering Antioxidant Grape Seed-Derived Polyphenol Compounds: A Potential Application in Aquaculture

“…Regarding DSC thermograms (Figure 4a), the GSE-SLN (6mg) -adsorbing GSE thermogram is the only one where small endothermic peaks at 114 • C and 118 • C are shown, and as pure GSE melting point is at 160 • C, they can be attributed to the shift of the endothermal peak of the extract because the esothermal peak at 160 • C resembles one of the Gelucire ® 50/13/Precirol ® ATO5 blends. Furthermore, as previously seen for the SLN containing GSE based on pure Gelucire ® 50/13 [2], in the DSC thermograms of GSE-SLN (6mg) and GSE-SLN (12mg) , no peak ascribable to GSE was detected (Figure 4b,d), suggesting that the molecular encapsulation of the extract occurred in these formulations. In the range 47-56 • C, either in the unloaded SLN or in GSE-containing SLN, endothermal signals were recorded, and they can be attributed to the Gelucire ® 50/13/Precirol ® ATO5 mixture.…”

“…As for the zeta potential of these nanocarriers, they resulted in the range −25.6-−43.4 mV indicative of a good colloidal stability. Furthermore, from the data reported in Table 1, high percentages of GSE entrapment were obtained (i.e., 49.7-74.6%) via the use of a lipid matrix where Gelucire ® 50/13 and Precirol ® ATO5 were combined and, notably, the GSE-SLN (6mg) -adsorbing GSE formulation was found to be the one loading the highest amount of the GSE mixture in comparison with our previous work [2]. As shown in Figure 2, to visualize SLN administering GSE, transmission electron spectroscopy (TEM) morphology was examined (Figure 2), and in the case of GSE-SLN (6mg) , an oval shape (Figure 2a) was detected rather than the spherical shape of GSE-SLN (6mg) -adsorbing GSE (Figure 2b).…”

“…Apart from single antioxidant molecules such as vitamin E and glutathione, which are already included in fish diet protocols, natural mixtures that include antioxidant compounds can also be of interest for fish nutrition if they are adopted as an entire extract without any separation of the active principles. In this context, we previously studied a mixture based on Apulian grape seed extract (GSE) for its favorable antioxidant and anti-inflammatory effects in human cells due to the relevant pro-anthocyanidin and polyphenol content (Figure 1; in [1,2]). With regard to pro-anthocyanidins contained in GSE, previous studies in the area of fish immunology Molecules 2022, 27, 344 2 of 21 elucidated that, once excessive fat accumulation takes place in fish, with consequent hepatic lipid metabolism disorder, then GSE allows hypolipidemic and potential anti-inflammatory effects in the liver, as occurred, for instance, in grass carp [3].…”

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose-to-Brain Delivery Application

“…In addition, if a sustained release of DA can be achieved in vivo by replacing L-Dopa administrations [49], a reduction in the toxic effects of L-Dopa can be expected, due to the fact that they typically emerge at later stages of PD. Overall, in view of nose-to-brain delivery, mean particle size of AlgOX-DA (Table 2) seems promising for bypassing the BBB because, as with colloidal carriers aiming at such non-invasive absorption approach, it has already been discussed that 200 nm is regarded as a suitable value for mean diameter [50,51].…”

In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN)

“…These results showed that tacrine-loaded NLC is safe for neuronal cells, being a promising formulation for the management of Alzheimer’s disease. Trapani et al [ 74 ] compared the in vitro cytotoxicity of grape seed-derived extract dopamine-loaded SLN, dopamine-loaded SLN and grape seed-derived extract-loaded SLN. The conjugation of dopamine with an antioxidant grape seed-derived proanthocyanidin reduces the oxidative stress observed in Parkinson’s disease.…”