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.

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid- and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis (ALS).

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.

Green compositions and processes for fabrication of dual-and multi-loaded nanocarriers with antioxidant functionality and neuroprotective, cardioprotective, antiviral, and antiproliferative activities are of broad interest for innovations in pharmaceutics and nutraceutics. Co-encapsulation of curcumin (studied as a key multipurpose phytochemical antioxidant) with ω-3 polyunsaturated fatty acids (PUFAs) (studied as active ingredients of natural fish oil) may increase the oxidative stability of selfassembled formulations aiming at development of "food drugs" and prevention of disease progression in various pathological states. The objective of this work is to prepare selfassembled lyotropic liquid crystalline nanostructures as dual-loaded biodegradable carriers of ω-3 PUFA-fish oil and curcumin. A detailed structural phase diagram of ternary [monoolein (MO) -PEGylated lipid mixture] / [fish oil -curcumin] / water system is created. A composition-mediated switch between nanostructures of different topologies and polymorphic states is achieved through varying the ratios between the amphiphilic monoglyceride ingredient, fish oil and water, which yielded cubic, sponge, and lamellar mesophases of tunable nanoscale repeat spacings. Synchrotron small-angle X-ray scattering (SAXS) studies are performed with the lyotropic liquid crystalline nanostructures along compositional dilution lines. The temperature effect is examined at 22 °C and 5 °C with regard to preparation conditions and mesophase stability on storage.Bulk mesophases are dispersed into lipid nanoparticles at 22 °C, the structures and topologies of which are revealed by SAXS and cryo-transmission electron microscopy (cryo-TEM) imaging. The new knowledge about the controlled multicomponent 3 supramolecular assembly and the achieved stabilization of low-temperature cubic phases (hydrated in 5 wt% D-(+)-glucose) should facilitate the development of cost-effective stable and safe delivery systems of weakly soluble natural antioxidant compounds coencapsulated with ω-3 PUFA oils.

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Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide–drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid-and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis (ALS).

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid-and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis (ALS).