Nanotechnology and COVID-19 Convergence: Toward New Planetary Health Interventions Against the Pandemic.

COVID-19 is a systemic disease affecting multiple organ systems and caused by infection with the SARS-CoV-2 virus. Two years into the COVID-19 pandemic and after the introduction of several vaccines, the pandemic continues to evolve in part owing to global inequities in access to preventive and therapeutic measures. We are also witnessing the introduction of antivirals against COVID-19. Against this current background, we review the progress made with nanotechnology-based approaches such as nanoformulations to combat the multiorgan effects of SARS-CoV-2 infection from a systems medicine lens. While nanotechnology has previously been widely utilized in the antiviral research domain, it has not yet received the commensurate interest in the case of COVID-19 pandemic response strategies. Notably, SARS-CoV-2 and nanomaterials are similar in size ranging from 50 to 200 nm. Nanomaterials offer the promise to reduce the side effects of antiviral drugs, codeliver multiple drugs while maintaining stability in the biological milieu, and sustain the release of entrapped drug(s) for a predetermined time period, to name but a few conceivable scenarios, wherein nanotechnology can enable and empower preventive medicine and therapeutic innovations against SARS-CoV-2. We conclude the article by underlining that nanotechnology-based interventions warrant further consideration to enable precision planetary health responses against the COVID-19 pandemic.

Nanoformulations targeting immune cells for cancer therapy: mRNA therapeutics

The approved worldwide use of two messenger RNA (mRNA) vaccines (BNT162b2 and mRNA-1273) in late 2020 has proven the remarkable success of mRNA therapeutics together with lipid nanoformulation technology in protecting people against coronaviruses during COVID-19 pandemic. This unprecedented and exciting dual strategy with nanoformulations and mRNA therapeutics in play is believed to be a promising paradigm in targeted cancer immunotherapy in future. Recent advances in nanoformulation technologies play a prominent role in adapting mRNA platform in cancer treatment. In this review, we introduce the biologic principles and advancements of mRNA technology, and chemistry fundamentals of intriguing mRNA delivery nanoformulations. We discuss the latest promising nano-mRNA therapeutics for enhanced cancer immunotherapy by modulation of targeted specific subtypes of immune cells, such as dendritic cells (DCs) at peripheral lymphoid organs for initiating mRNA cancer vaccine-mediated antigen specific immunotherapy, and DCs, natural killer (NK) cells, cytotoxic T cells, or multiple immunosuppressive immune cells at tumor microenvironment (TME) for reversing immune evasion. We highlight the clinical progress of advanced nano-mRNA therapeutics in targeted cancer therapy and provide our perspectives on future directions of this transformative integrated technology toward clinical implementation.

Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery.

Remdesivir is the only clinically available antiviral drug for the treatment of COVID-19. However, its very limited aqueous solubility confines its therapeutic activity and the development of novel inhaled nano-based drug delivery systems of remdesivir for enhanced lung tissue targeting and efficacy is internationally pursued. In this work 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) hyperbranched dendritic nano-scaffolds were employed as nanocarriers of remdesivir. The produced nano-formulations, empty and loaded, consisted of monodisperse nanoparticles with spherical morphology and neutral surface charge and sizes ranging between 80 and 230 nm. The entrapment efficiency and loading capacity of the loaded samples were 82.0% and 14.1%, respectively, whereas the release of the encapsulated drug was complete after 48 h. The toxicity assays in healthy MRC-5 lung diploid fibroblasts and NR8383 alveolar macrophages indicated their suitability as potential remdesivir carriers in the respiratory system. The novel nano-formulations are non-toxic in both tested cell lines, with IC50 values higher than 400 µΜ after 72 h treatment. Moreover, both free and encapsulated remdesivir exhibited very similar IC50 values, at the range of 80-90 µM, while its aqueous solubility was increased, overall presenting a suitable profile for application in inhaled delivery of therapeutics.

Pulmonary Delivery of Hydroxychloroquine Nanostructured Lipid Carrier as a Potential Treatment of COVID-19.

Coronavirus Disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2. Pneumonia is considered the most severe and long-term complication of COVID-19. Among other drugs, hydroxychloroquine (HCQ) was repurposed for the management of COVID-19; however, low efficacy and cardiac toxicity of the conventional dosage form limited its use in COVID-19. Therefore, utilizing nanotechnology, a pulmonary delivery system of HCQ was investigated to overcome these limitations. HCQ was formulated in nanostructured lipid carriers (HCQ-NLCs) using the hot emulsification-ultrasonication method. Furthermore, the prepared formulation was evaluated in vitro. Moreover, the efficacy was tested in vivo in a bleomycin-induced acute lung injury mice model. Intriguingly, nanoformulations were given by the intratracheal route for 6 days. HCQ-NLCs showed a mean particle size of 277 nm and a good drug release profile. Remarkably, acute lung injury induced by bleomycin was associated with a marked elevation of inflammatory markers and histological alterations in lung tissues. Astoundingly, all these changes were significantly attenuated with HCQ-NLCs. The pulmonary delivery of HCQ-NLCs likely provided adequate targeting to lung tissues. Nevertheless, there is hope that this novel strategy will eventually lead to the improved effectiveness and diminished probability of alarming adverse drug reactions.

When Scent Becomes a Weapon—Plant Essential Oils as Potent Bioinsecticides

Crop protection still mostly relies on synthetic pesticides for crop pest control. However, the rationale for their continued use is shaded by the revealed adverse effects, such as relatively long environmental persistence that leads to water and soil contamination and retention of residues in food that brings high risks to human and animal health. As part of integrated pest management, biopesticides may provide crop protection, being eco-friendly and safe for humans and non-target organisms. Essential oils, complex mixtures of low-molecular-weight, highly volatile compounds, have been highlighted as major candidates for plant-derived bioinsecticides that are up to the sustainable biological standard. In this review, we screened the insecticidal activity of essential oils or their purified compounds, with focus given to their modes of action, along with the analyzed advantages and problems associated with their wider usage as plant-derived insecticides in agriculture.

Bioactive Based Nanocarriers for the Treatment of Viral Infections and SARS-CoV-2.

Since ancient times, plants have been used for their medicinal properties. They provide us with many phytomolecules, which serve a synergistic function for human well-being. Along with anti-microbial, plants also possess anti-viral activities. In Western nations, about 50% of medicines were extracted from plants or their constituents. The spread and pandemic of viral diseases are becoming a major threat to public health and a burden on the financial prosperity of communities worldwide. In recent years, SARS-CoV-2 has made a dramatic lifestyle change. This has promoted scientists not to use synthetic anti-virals, such as protease inhibitors, nucleic acid analogs, and other anti-virals, but to study less toxic anti-viral phytomolecules. An emerging approach includes searching for eco-friendly therapeutic molecules to develop phytopharmaceuticals. This article briefly discusses numerous bioactive molecules that possess anti-viral properties, their mode of action, and possible applications in treating viral diseases, with a special focus on coronavirus and various nano-formulations used as a carrier for the delivery of phytoconstituents for improved bioavailability.

The Natural Product Curcumin as an Antibacterial Agent: Current Achievements and Problems.

The rapid spread of antibiotic resistance and lack of effective drugs for treating infections caused by multi-drug resistant bacteria in animal and human medicine have forced us to find new antibacterial strategies. Natural products have served as powerful therapeutics against bacterial infection and are still an important source for the discovery of novel antibacterial drugs. Curcumin, an important constituent of turmeric, is considered safe for oral consumption to treat bacterial infections. Many studies showed that curcumin exhibited antibacterial activities against Gram-negative and Gram-positive bacteria. The antibacterial action of curcumin involves the disruption of the bacterial membrane, inhibition of the production of bacterial virulence factors and biofilm formation, and the induction of oxidative stress. These characteristics also contribute to explain how curcumin acts a broad-spectrum antibacterial adjuvant, which was evidenced by the markedly additive or synergistical effects with various types of conventional antibiotics or non-antibiotic compounds. In this review, we summarize the antibacterial properties, underlying molecular mechanism of curcumin, and discuss its combination use, nano-formulations, safety, and current challenges towards development as an antibacterial agent. We hope that this review provides valuable insight, stimulates broader discussions, and spurs further developments around this promising natural product.

Nanotechnology: A Potential Weapon to Fight against COVID-19.

The COVID-19 infections have posed an unprecedented global health emergency, with nearly three million deaths to date, and have caused substantial economic loss globally. Hence, an urgent exploration of effective and safe diagnostic/therapeutic approaches for minimizing the threat of this highly pathogenic coronavirus infection is needed. As an alternative to conventional diagnosis and antiviral agents, nanomaterials have a great potential to cope with the current or even future health emergency situation with a wide range of applications. Fundamentally, nanomaterials are physically and chemically tunable and can be employed for the next generation nanomaterial-based detection of viral antigens and host antibodies in body fluids as antiviral agents, nanovaccine, suppressant of cytokine storm, nanocarrier for efficient delivery of antiviral drugs at infection site or inside the host cells, and can also be a significant tool for better understanding of the gut microbiome and SARS-CoV-2 interaction. The applicability of nanomaterial-based therapeutic options to cope with the current and possible future pandemic is discussed here.

A comprehensive review of the therapeutic potential of curcumin nanoformulations.

Today, due to the prevalence of various diseases such as the novel coronavirus (SARS-CoV-2), diabetes, central nervous system diseases, cancer, cardiovascular disorders, and so on, extensive studies have been conducted on therapeutic properties of natural and synthetic agents. A literature review on herbal medicine and commercial products in the global market showed that curcumin (Cur) has many therapeutic benefits compared to other natural ingredients. Despite the unique properties of Cur, its use in clinical trials is very limited. The poor biopharmaceutical properties of Cur such as short half-life in plasma, low bioavailability, poor absorption, rapid metabolism, very low solubility (at acidic and physiological pH), and the chemical instability in body fluids are major concerns associated with the clinical applications of Cur. Recently, nanoformulations are emerging as approaches to develop and improve the therapeutic efficacy of various drugs. Many studies have shown that Cur nanoformulations have tremendous therapeutic potential against various diseases such as SARS-CoV-2, cancer, inflammatory, osteoporosis, and so on. These nanoformulations can inhibit many diseases through several cellular and molecular mechanisms. However, successful long-term clinical results are required to confirm their safety and clinical efficacy. The present review aims to update and explain the therapeutic potential of Cur nanoformulations.

Regulatory status quo and prospects for biosurfactants in pharmaceutical applications.

The concept of going 'green' and 'cold' has led to utilizing renewable resources for the synthesis of microbial biosurfactants that are both patient and eco-friendly. In this review, we shed light on the potential and regulatory aspects of biosurfactants in pharmaceutical applications and how they can significantly contribute to novel concepts for the Coronavirus 2019 (COVID-19) vaccine and future treatment. We emphasize that more specific guidelines should be formulated to regulate the approval of biosurfactants for human use. It is also crucial to implement a risk-based approach from the early research and development (R&D) phase in addition to establishing more robust standardized techniques and assays to evaluate the characteristics of biosurfactants.

A bird eye view on cystic fibrosis: An underestimated multifaceted chronic disorder.

Cystic fibrosis (CF) is an autosomal recessive disease which involves the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF involves in the inflammatory processes and is considered as a multisystem disorder that is not confined to lungs, but it also affects other vital organs that leads to numerous co-morbidities. The respiratory disorder in the CF results in mortality and morbidity which is characterized by series of serious events involving mucus hypersecretion, microbial infections, airways obstruction, inflammation, destruction of epithelium, tissue remodeling and terminal lung diseases. Mucins are the high molecular weight glycoproteins important for the viscoelastic properties of the mucus, play a significant role in the disease mechanisms. Determining the functional association between the CFTR and mucins might help to identify the putative target for specific therapeutic approach. In fact, furin enzyme which helps in the entry of novel COVID-19 virus into the cell, is upregulated in CF and this can also serve as a potential target for CF treatment. Moreover, the use of nano-formulations for CF treatment is an area of research being widely studied as they have also demonstrated promising outcomes. The in-depth knowledge of non-coding RNAs like miRNAs and lncRNAs and their functional association with CFTR gene expression and mutation can provide a different range of opportunity to identify the promising therapeutic approaches for CF.

Lectin Protein as a Promising Component to Functionalize Micelles, Liposomes and Lipid NPs against Coronavirus.

The outbreak of a novel strain coronavirus as the causative agent of COVID-19 pneumonia, first identified in Wuhan, China in December 2019, has resulted in considerable focus on virulence abilities of coronavirus. Lectins are natural proteins with the ability to bind specific carbohydrates related to various microorganisms, including viruses, bacteria, fungi and parasites. Lectins have the ability to agglutinate and neutralize these pathogeneses. The delivery of the encapsulated antiviral agents or vaccines across the cell membrane can be possible by functionalized micellar and liposomal formulations. In this mini-review, recent advances and challenges related to important lectins with inhibition activities against coronaviruses are presented to obtain a novel viewpoint of microformulations or nanoformulations by micellar and liposomal cell-binding carriers.

Potential of Nanonutraceuticals in Increasing Immunity.

Nutraceuticals are defined as foods or their extracts that have a demonstrably positive effect on human health. According to the decision of the European Food Safety Authority, this positive effect, the so-called health claim, must be clearly demonstrated best by performed tests. Nutraceuticals include dietary supplements and functional foods. These special foods thus affect human health and can positively affect the immune system and strengthen it even in these turbulent times, when the human population is exposed to the COVID-19 pandemic. Many of these special foods are supplemented with nanoparticles of active substances or processed into nanoformulations. The benefits of nanoparticles in this case include enhanced bioavailability, controlled release, and increased stability. Lipid-based delivery systems and the encapsulation of nutraceuticals are mainly used for the enrichment of food products with these health-promoting compounds. This contribution summarizes the current state of the research and development of effective nanonutraceuticals influencing the body's immune responses, such as vitamins (C, D, E, B12, folic acid), minerals (Zn, Fe, Se), antioxidants (carotenoids, coenzyme Q10, polyphenols, curcumin), omega-3 fatty acids, and probiotics.