Curcumin- and Fish Oil-Loaded Spongosome and Cubosome Nanoparticles with Neuroprotective Potential against H₂O₂-Induced Oxidative Stress in Differentiated Human SH-SY5Y Cells

Abstract

Many phytochemical antioxidant compounds, including curcumin (CU), are water-insoluble and thus require delivery carriers in order to increase their bioavailability for in vivo applications. Oxidative stress-related apoptosis is a common cause for the neuronal loss in the progression of neurodegenerative diseases. Lipid nanoparticles (NPs) with internal self-assembled liquid crystalline structures present strong interest as safe drug delivery systems for neuronal regeneration through combination therapies. Here, we report spongosome and cubosome lipid NPs, which co-encapsulate CU and fish oil (FO), rich in ω-3 polyunsaturated fatty acids. The performed structural investigation by synchrotron small-angle X-ray scattering evidenced the liquid crystalline organization of the self-assembled NPs. The encapsulation efficiency for CU in the lipid nanocarriers was found to be higher as compared to that reported for polymer-based carriers. The cytotoxicity of the blank and antioxidant-loaded nanocarriers was negligible at lipid concentrations 300 and 500 nM. Morphological changes were observed for neuronally derived human SH-SY5Y cells subjected to damage by reactive oxygen species (ROS) upon exposure to hydrogen peroxide. Using flow cytometry, we quantified the effects of CU and FO, co-encapsulated in spongosome and cubosome lipid NPs on the response of differentiated SH-SY5Y cells to H 2 O 2 -induced oxidative stress. Measurements of the intracellular ROS levels (using a 2′,7′dichlorodihydrofluorescein diacetate probe) and of apoptotic cells (using an Annexin V-PE/SYTOX-green assay) were performed to compare the neuroprotective potential of the liquid crystalline spongosome and cubosome nanocarriers to that of ethanolic solutions or aqueous suspensions of the CU/FO mixtures. The results indicated that dual drug-loaded cubosomes may be suitable for combination treatments against neurodegenerative disorders.(1) Brookmeyer, R.; Abdalla, N.; Kawas, C. H.; Corrada, M. M. Forecasting the prevalence of preclinical and clinical Alzheimer's disease in the United States.

Pep‐Lipid Cubosomes and Vesicles Compartmentalized by Micelles from Self‐Assembly of Multiple Neuroprotective Building Blocks Including a Large Peptide Hormone PACAP‐DHA

“…Despite of the reported variety of nanoparticulate assemblies of liquid crystalline order and hierarchical complexity, the investigations in which the structural organization of the lipid nanocarriers has been suggested as beneficial for curing of neurodegenerative disorders are scarce . The modifications of GPCR ligands and other neuropeptides by lipophilic anchors is suggested as a possibility for enhancement of the neuropeptide drug bioavailability.…”

“…Our structural approach includes BioSAXS investigations of the nanostructures resulting from the self‐assembly of the amphiphile of major interest PACAP‐DHA alone and in mixtures with additional safe compounds (Figure ) that may yield hybrid assemblies with compartmentalized organization involving bilayer building blocks. To ensure the steric stability of the dispersed nanoparticles, we included in the assemblies the PEGylated amphiphile vitamin E α‐tocopheryl polyethylene glycol 1000 succinate (VPGS‐PEG 1000 ), which has been known as a safe surfactant . Preliminary BioSAXS experiments have established that PACAP‐DHA has no strong affinity for assembly with VPGS‐PEG 1000 micelles used as a single‐component biomimetic membrane medium.…”

Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

“…Values <5 mV may lead to agglomeration of particles conferring physical instability in solution. On the contrary, Z-potential >30 mV, either positive or negative, leads to monodispersity and good physical stability in solution [45,46] Finally, high positive Z-potential values are correlated to high cytotoxicity while negative values allow high cell viability [47]. In this regards, the CPX 5 nanoparticles that proved to possess a Z-potential of −45 mV ± SD can be rationally considered stable in water solution, with no tendency to form aggregates and are endowed with low cytotoxicity.…”

“…Nanoparticles are extensively inspected to prepare multifunctional smart materials [26][27][28][29][30] and are widely employed in various biomedical applications [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49].…”

Non-Lamellar Liquid Crystalline Nanocarriers for Thymoquinone Encapsulation

“…Taking into account the current interest in the development of nanocarriers for delivering TQ and other phytochemicals [8][9][10][11][15][16][17][18][19][20][21], here we focus on non-lamellar liquid crystalline nanoparticles enveloping a biphasic feature of inverse discontinuous cubic (I 2 ) phase of the symmetry Fd3m phase coexisting with an inverse hexagonal (H 2 ) phase for TQ encapsulation. The unique structural properties of these nano-self-assemblies and their analogues [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] render them particularly attractive for enhancing the solubilization capacity of poorly water-soluble drugs and improving their delivery through different routes of administration [23,26,27,29,36]. However, the structural features of this family of liquid crystalline nanoparticles is highly sensitive to drug loading, and subsequently could affect its stability as well as biological performance.…”