ABSTRACT
The actual cumulative mass of released quercetin from nanoparticles within the dialysis membrane was determined under the influence of external stationary and alternating magnetic fields. We have shown that the control of the release kinetics of quercetin from MNPs, i.e., the distribution of quercetin between the nanoparticles and the suspension within the membrane, can be tuned by the simple combination of stationary and alternating magnetic fields. Under non-sink conditions, the proportion of quercetin in the suspension inside the membrane is increased toward the nanoparticles, resulting in the increased release of quercetin. The results obtained could be applied to the release of insoluble flavonoids in aqueous suspensions in general.
ABSTRACT
Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related to oxidative stress (OS) and neuroinflammation are particularly important. Here, we provide a brief overview of the key concepts related to OS- and neuroinflammation-mediated neuropathological changes in neurodegeneration, together with the role of transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB). This review is focused on the transcription factor p53 that coordinates the cellular response to diverse genotoxic stimuli, determining neuronal death or survival. As current pharmacological options in the treatment of neurodegenerative disease are only symptomatic, many research efforts are aimed at uncovering efficient disease-modifying agents. Natural polyphenolic compounds demonstrate powerful anti-oxidative, anti-inflammatory and anti-apoptotic effects, partially acting as modulators of signaling pathways. Herein, we review the current understanding of the therapeutic potential and limitations of flavonols in neuroprotection, with emphasis on their anti-oxidative, anti-inflammatory and anti-apoptotic effects along the Nrf2, NF-κB and p53 pathways. A better understanding of cellular and molecular mechanisms of their action may pave the way toward new treatments.
ABSTRACT
Superparamagnetic magnetite nanoparticles (MNPs) with excellent biocompatibility and negligible toxicity were prepared by solvothermal method and stabilized by widely used and biocompatible polymer poly(ethylene glycol) PEG-4000 Da. The unique properties of the synthesized MNPs enable them to host the unstable and water-insoluble quercetin as well as deliver and localize quercetin directly to the desired site. The chemical and physical properties were validated by X-ray powder diffraction (XRPD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), superconducting quantum interference device (SQUID) magnetometer, FTIR spectroscopy and dynamic light scattering (DLS). The kinetics of in vitro quercetin release from MNPs followed by UV/VIS spectroscopy was controlled by employing combined stationary and alternating magnetic fields. The obtained results have shown an increased response of quercetin from superparamagnetic MNPs under a lower stationary magnetic field and s higher frequency of alternating magnetic field. The achieved findings suggested that we designed promising targeted quercetin delivery with fine-tuning drug release from magnetic MNPs.
ABSTRACT
Flavonoids, polyphenols with anti-oxidative activity have high potential as novel therapeutics for neurodegenerative disease, but their applicability is rendered by their poor water solubility and chemical instability under physiological conditions. In this study, this is overcome by delivering flavonoids to model cell membranes (unsaturated DOPC) using prepared and characterized biodegradable mesoporous silica nanoparticles, MSNs. Quercetin, myricetin and myricitrin have been investigated in order to determine the relationship between flavonoid structure and protective activity towards oxidative stress, i.e., lipid peroxidation induced by the addition of hydrogen peroxide and/or Cu2+ ions. Among investigated flavonoids, quercetin showed the most enhanced and prolonged protective anti-oxidative activity. The nanomechanical (Young modulus) measurement of the MSNs treated DOPC membranes during lipid peroxidation confirmed attenuated membrane damage. By applying a combination of experimental techniques (atomic force microscopy-AFM, force spectroscopy, electrophoretic light scattering-ES and dynamic light scattering-DLS), this work generated detailed knowledge about the effects of flavonoid loaded MSNs on the elasticity of model membranes, especially under oxidative stress conditions. Results from this study will pave the way towards the development of innovative and improved markers for oxidative stress-associated neurological disorders. In addition, the obtained could be extended to designing effective delivery systems of other high potential bioactive molecules with an aim to improve human health in general.
