Some biologically active substances are unstable and poorly soluble in aqueous media, at the same time exhibiting low bioavailability. The incorporation of these biologically active compounds into the structure of a lipid-based lyotropic liquid crystalline phase or nanoparticles can increase or improve their stability and transport properties, subsequent bioavailability, and applicability in general. The aim of this short overview is (1) to clarify the principle of self-assembly of lipidic amphiphilic molecules in an aqueous environment and (2) to present lipidic bicontinuous cubic and hexagonal phases and their current biosensing (with a focus on electrochemical protocols) and biomedical applications.

• Klíčová slova
• Biologically active compounds, Cubosome, Hexosome, Lipidic cubic phase, Lipidic nanoparticles,
• MeSH
• kapalné krystaly * chemie   MeSH
• lipidy chemie   MeSH
• nanočástice * chemie   MeSH
• technologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• lipidy MeSH

Lipid nitroalkenes - nitro-fatty acids (NO2-FAs) are formed in vivo via the interaction of reactive nitrogen species with unsaturated fatty acids. The resulting electrophilic NO2-FAs play an important role in redox homeostasis and cellular stress response. This study investigated the physicochemical properties and reactivity of two NO2-FAs: 9/10-nitrooleic acid (1) and its newly prepared 1-monoacyl ester, (E)-2,3-hydroxypropyl 9/10-nitrooctadec-9-enoate (2), both synthesized by a direct radical nitration approach. Compounds 1 and 2 were investigated in an aqueous medium and after incorporation into lipid nanoparticles prepared from 1-monoolein, cubosomes 1@CUB and 2@CUB. Using an electrochemical analysis and LC-MS, free 1 and 2 were found to be unstable under acidic conditions, and their degradation occurred in an aqueous environment within a few minutes or hours. This degradation was associated with the production of the NO radical, as confirmed by fluorescence assay. In contrast, preparations 1@CUB and 2@CUB exhibited a significant increase in the stability of the loaded 1 and 2 up to several days to weeks. In addition to experimental data, density functional theory-based calculation results on the electronic structure and structural variability (open and closed configuration) of 1 and 2 were obtained. Finally, experiments with a human HaCaT keratinocyte cell line demonstrated the ability of 1@CUB and 2@CUB to penetrate through the cytoplasmic membrane and modulate cellular pathways, which was exemplified by the Keap1 protein level monitoring. Free 1 and 2 and the cubosomes prepared from them showed cytotoxic effect on HaCaT cells with IC50 values ranging from 1 to 8 μM after 24 h. The further development of cubosomal preparations with embedded electrophilic NO2-FAs may not only contribute to the field of fundamental research, but also to their application using an optimized lipid delivery vehicle.

• Klíčová slova
• Cubosome, Keratinocytes, Lipidic mesophase, Monoacyl glycerol, Nitric oxide, Nitrooleate,
• MeSH
• dusíkaté sloučeniny MeSH
• faktor 2 související s NF-E2 MeSH
• KEAP-1 MeSH
• lidé MeSH
• mastné kyseliny * MeSH
• oxid dusnatý * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dusíkaté sloučeniny MeSH
• faktor 2 související s NF-E2 MeSH
• KEAP-1 MeSH
• mastné kyseliny * MeSH
• oxid dusnatý * MeSH

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.

• Klíčová slova
• BioSAXS, catalase, cubosome, curcumin, fish oil, liquid crystalline nanoparticles, peroxidatic activity of catalase,
• MeSH
• kapalné krystaly chemie   MeSH
• katalasa chemie   MeSH
• kurkumin chemie   MeSH
• lidé MeSH
• maloúhlový rozptyl MeSH
• nanostruktury chemie   MeSH
• peroxid vodíku chemie   MeSH
• polyethylenglykoly chemie   MeSH
• reaktivní formy kyslíku MeSH
• synchrotrony MeSH
• zobrazování trojrozměrné MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• katalasa MeSH
• kurkumin MeSH
• peroxid vodíku MeSH
• polyethylene glycol 1000 MeSH Prohlížeč
• polyethylenglykoly MeSH
• reaktivní formy kyslíku MeSH

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are bioactive lipids with considerable impact in medicine and nutrition. These compounds exert structuring effects on the cellular membrane organization, regulate the gene expression, and modulate various signaling cascades and metabolic processes. The purpose of the present work is to demonstrate the structural features of ω-3 PUFA-containing three-dimensional supramolecular lipid assemblies suitable for pharmaceutical applications that require soft porous carriers. We investigate the liquid crystalline structures formed upon mixing of eicosapentaenoic acid (EPA, 20:5) with the lyotropic nonlamellar lipid monoolein and the formation of multicompartment assemblies. Starting with the monoolein-based lipid cubic phase, double membrane vesicles, cubosome precursors, sponge-type particles (spongosomes), mixed intermediate nonlamellar structures, and multicompartment assemblies are obtained through self-assembly at different amphiphilic compositions. The dispersions containing spongosomes as well as nanocarriers with oil and vesicular compartments are stabilized by PEGylation of the lipid/water interfaces using a phospholipid with a poly(ethylene glycol) chain. The microstructures of the bulk mixtures were examined by cross-polarized light optical microscopy. The dispersed liquid crystalline structures and intermediate states were studied by small-angle X-ray scattering, cryogenic transmission electron microscopy, and quasielastic light scattering techniques. They established that PUFA influences the phase type and the sizes of the aqueous compartments of the liquid crystalline carriers. The resulting multicompartment systems and stealth nanosponges may serve as mesoporous reservoirs for coencapsulation of ω-3 PUFA (e.g., EPA) with water-insoluble drugs and hydrophilic macromolecules toward development of combination treatment strategies of neurodegenerative and other diseases.

• Publikační typ
• časopisecké články MeSH