Cubic Liquid Crystalline Nanostructures Involving Catalase and Curcumin: BioSAXS Study and Catalase Peroxidatic Function after Cubosomal Nanoparticle Treatment of Differentiated SH-SY5Y Cells

Abstract

The development of nanomedicines for the treatment of neurodegenerative disorders demands innovative nanoarchitectures for combined loading of multiple neuroprotective compounds. We report dual-drug loaded monoolein-based liquid crystalline architectures designed for the encapsulation of a therapeutic protein and a small molecule antioxidant. Catalase (CAT) is chosen as a metalloprotein, which provides enzymatic defense against oxidative stress caused by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Curcumin (CU), solubilized in fish oil, is co-encapsulated as a chosen drug with multiple therapeutic activities, which may favor neuro-regeneration. The prepared self-assembled biomolecular nanoarchitectures are characterized by biological synchrotron small-angle X-ray scattering (BioSAXS) at multiple compositions of the lipid/co-lipid/water phase diagram. Constant fractions of curcumin (an antioxidant) and a PEGylated agent (TPEG1000) are included with regard to the lipid fraction. Stable cubosome architectures are obtained for several ratios of the lipid ingredients monoolein (MO) and fish oil (FO). The impact of catalase on the structural organization of the cubosome nanocarriers is revealed by the variations of the cubic lattice parameters deduced by BioSAXS. The outcome of the cellular uptake of the dual drug-loaded nanocarriers is assessed by performing a bioassay of catalase peroxidatic activity in lysates of nanoparticle-treated differentiated SH-SY5Y human cells. The obtained results reveal the neuroprotective potential of the in vitro studied cubosomes in terms of enhanced peroxidatic activity of the catalase enzyme, which enables the inhibition of H2O2 accumulation in degenerating neuronal cells.

Plasmalogen-Based Liquid Crystalline Multiphase Structures Involving Docosapentaenoyl Derivatives Inspired by Biological Cubic Membranes

“…Nanoparticles and nanoassemblies may offer innovative combinations of multiple bioactive molecules to target the various mechanisms of multiple neurodegenerative diseases ( Angelova et al, 2011 , 2019b ; Fonseca-Santos et al, 2015 ; Angelova and Angelov, 2017 ; Harilal et al, 2019 ). In recent works, we have exploited self-assembly-based nanotechnologies for combination delivery of a key neurotrophic protein [brain-derived neurotrophic factor (BDNF)], curcumin, and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in order to trigger and promote neuro-repair ( Guerzoni et al, 2017 ; Angelova et al, 2018 ; Rakotoarisoa et al, 2019 ). Biomedical studies have emphasized that AD patients lose up to 60% of plasmalogens from the brain cell membranes ( Farooqui et al, 1997 ; Su et al, 2019 ).…”

Dim Light at Night Induced Neurodegeneration and Ameliorative Effect of Curcumin

“…Even though the bioavailability of curcumin is restricted by the blood–brain barrier, many researchers had reported its highly effective therapeutic ability in the brain disorders including Alzheimer’s, Parkinson’s, and Huntington’s diseases; multiple sclerosis; depression; and schizophrenia [ 28 , 29 , 30 , 31 ]. With advancement in the field of researcher, the bioavailability of curcumin has been improved tremendously through the development of nano-particle-encapsulated curcumin administration [ 32 , 33 , 34 , 35 ]. In addition, its oral administration has been found to improve the learning and memory in animal models [ 36 , 37 , 38 , 39 , 40 , 41 ].…”

Curcumin Containing PEGylated Solid Lipid Nanoparticles for Systemic Administration: A Preliminary Study

“…Curcumin (diferuloylmethane; CUR) is an active compound, extracted from rhizomes by Curcuma Longa , which has shown excellent therapeutic properties for the treatment of various diseases [ 1 , 2 , 3 , 4 , 5 ]. CUR is an excellent antioxidant that is able to prevent or slow down damage to cells caused by free radicals, as well as reactive oxygen species (ROS) and reactive nitrogen species (RNS) [ 6 ].…”