Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome.

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.

Antioxidants for improved skin appearance: Intracellular mechanism, challenges and future strategies.

Recent advances in molecular and biochemical processes relevant to the skincare field have led to the development of novel ingredients based on antioxidants that can improve skin health and youthfulness. Considering the plethora of such antioxidants and the many implications for the skin's appearance, this review focuses on describing the critical aspects of antioxidants, including cosmetic functions, intracellular mechanisms and challenges. In particular, specialized substances are suggested for the treatment of each skin condition, such as skin ageing, skin dehydration and skin hyperpigmentation, which treatments can maximize effectiveness and avoid side effects during skin care processes. In addition, this review proposes advanced strategies that either already exists in the cosmetic market or should be developed to improve and optimize cosmetic' beneficial effects.

Les progrès récents des processus moléculaires et biochimiques pertinents pour le domaine des soins de la peau ont conduit au développement de nouveaux ingrédients à base d'antioxydants qui peuvent améliorer la santé et la jeunesse de la peau. Compte tenu de la pléthore de ces antioxydants et des nombreuses implications pour l'apparence de la peau, cette revue se concentre sur la description des aspects critiques des antioxydants, pour le domaine de la cosmétique, pour les mécanismes intracellulaires et les défis à surmonter. En particulier, des substances spécialisées sont suggérées pour le traitement de chaque affection cutanée, comme le vieillissement cutané, la déshydratation cutanée et l'hyperpigmentation cutanée, lesquels traitements peuvent maximiser l'efficacité et éviter les effets secondaires pendant les processus de soins de la peau. De plus, cette revue propose des stratégies avancées qui existent déjà sur le marché des cosmétiques ou qui devraient être développées pour améliorer et optimiser les effets bénéfiques des cosmétiques.

Applications of Antioxidants in Dental Procedures.

As people are paying more and more attention to dental health, various dental treatment procedures have emerged, such as tooth bleaching, dental implants, and dental restorations. However, a large number of free radicals are typically produced during the dental procedures. When the imbalance in distribution of reactive oxygen species (ROS) is induced, oxidative stress coupled with oxidative damage occurs. Oral inflammations such as those in periodontitis and pulpitis are also unavoidable. Therefore, the applications of exogenous antioxidants in oral environment have been proposed. In this article, the origin of ROS during dental procedures, the types of antioxidants, and their working mechanisms are reviewed. Additionally, antioxidants delivery in the complicated dental procedures and their feasibility for clinical applications are also covered. Finally, the importance of safety assessment of these materials and future work to take the challenge in antioxidants development are proposed for perspective.

Oxidative stress and diabetes: antioxidative strategies.

Diabetes mellitus is one of the major public health problems worldwide. Considerable recent evidence suggests that the cellular reduction-oxidation (redox) imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in ß-cell dysfunction and insulin resistance. Reactive oxide species (ROS) can also directly oxidize certain proteins (defined as redox modification) involved in the diabetes process. There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility, storage instability and nonselectivity of antioxidants. Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS. We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus. Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes.

Nanoantioxidants: Recent Trends in Antioxidant Delivery Applications.

Antioxidants interact with free radicals, terminating the adverse chain reactions and converting them to harmless products. Antioxidants thus minimize the oxidative stress and play a crucial role in the treatment of free radicals-induced diseases. However, the effectiveness of natural and/or synthetic antioxidants is limited due to their poor absorption, difficulties to cross the cell membranes, and degradation during delivery, hence contributing to their limited bioavailability. To address these issues, antioxidants covalently linked with nanoparticles, entrapped in nanogel, hollow particles, or encapsulated into nanoparticles of diverse origin have been used to provide better stability, gradual and sustained release, biocompatibility, and targeted delivery of the antioxidants with superior antioxidant profiles. This review aims to critically evaluate the recent scientific evaluations of nanoparticles as the antioxidant delivery vehicles, as well as their contribution in efficient and enhanced antioxidant activities.

Nanocarrier-based antioxidant therapy: promise or delusion?

INTRODUCTION: Oxidative stress has generally been recognized as an important factor in the pathogenesis of human diseases, making antioxidant therapy a plausible strategy to either prevent or treat human disorders. Yet so far, numerous antioxidant-based clinical trials aimed at developing clinically approved protocols have been disappointing and many reasons for their failure are being discussed, including the limited bioavailability of most antioxidants. To overcome the hurdles associated with the direct administration of antioxidant molecules, a variety of nanotechnology-based drug delivery systems are being developed. All the strategies currently being explored, however, appear in our opinion to underappreciate the crucial role reactive oxygen and nitrogen species (RO/NS) play in the regulation of the metabolome, as revealed by recent progress made in redox biology. AREAS COVERED: We briefly review antioxidant-based clinical trials and discuss the functions of RO/NS as crucial intracellular messengers. We emphasize the probable existence of three distinct concentration levels of RO/NS: a physiological level reflecting their functions as messenger molecules, an elevated level crucial for activation of protective pathways and a toxic level causing oxidative damage to cellular components. EXPERT OPINION: Site-specific, multifunctional nanodrug delivery systems able to sense the actual intracellular concentrations of RO/NS and release antioxidants accordingly in order to only neutralize the pathologic excess of RO/NS need to be developed.

New concepts to fight oxidative stress: nanosized three-dimensional supramolecular antioxidant assemblies.

INTRODUCTION: Misregulation of reactive oxygen species and reactive nitrogen species by the body's antioxidant system results in oxidative stress, which is known to be associated with aging, and involved in various pathologies including cancer, neurodegenerative and cardiovascular diseases. A large variety of low-molecular-weight (LMW) antioxidant compounds and antioxidant enzymes have been proposed to alleviate oxidative stress, but their therapeutic efficacy is limited by their solubility, stability or bioavailability. In this respect, nanoscience-based systems are expected to provide more efficient mitigation of oxidative stress. AREAS COVERED: The main nanoscience-based three-dimensional (3D) supramolecular assemblies, decorated with, or entrapping antioxidant compounds, or which possess intrinsic antioxidant activity are discussed and illustrated with recent examples. Assemblies with different architectures and sizes in the nanometer range serve: i) to deliver LMW antioxidant compounds or enzymes; ii) as antioxidant systems due to their intrinsic activity; and recently iii) to provide a confined space where catalytic antioxidant reactions take place in situ (nanoreactors and artificial organelles). A few insights into the role of antioxidants in mitigating oxidative stress caused by therapeutic compounds or drug carriers are also discussed. EXPERT OPINION: Several challenges must still be overcome in the development of 3D supramolecular assemblies to efficiently fight oxidative stress. First, an improvement of the assemblies' properties and stability in biological conditions has to be addressed. Second, new systems based on the combination of biomolecules or mimics in supramolecular assemblies should provide multifunctionality, stimuli-responsiveness and targeting properties for a more efficient therapeutic effect. Third, comparative studies are necessary to evaluate these systems in a standardized manner both in vitro and in vivo.