Antiviral and cytotoxic effects of a traditional drug KanthaRasaVillai with a cocktail of metallic nanoparticles.

OBJECTIVE: Alternative medicine plays an important role today in searching for therapeutics for cancer and viral infection. So, a scientific validation to characterize constituents in the alternative medicines and therapeutic testing is warranted using modern instrumentation. METHODS: In the present study, an old herbomineral formulation, KanthaRasavillai [KRV], was characterized using UV-vis spectrometry, FT-IR, XRD, SEM, and TEM study. Also, In vitro and in vivo studies were done to evaluate their antiviral and anticancer activity. FT-IR and XRD studies revealed a cocktail of nanoparticles of mercury, magnetic oxide, cinnabar, and arsenic.ResultsBased on SEM, TEM, and XRD report, KRV contains nanoparticles in the size range of 9.1nm to 25.0 nm. FT-IR analysis exposed the presence of several anti-cancerous bioactive compounds.Further in vitro testing against HCV virus proved KRV to inhibit HCV virus a close relative to SARS-CoV-2. MTT assay confirmed the anticancer effect of KRV against Huh-7 and MCF-7 cell lines. CONCLUSION: The anticancer and antiviral properties in the ancient herbomineral drug with a cocktail of metal nanoparticles acknowledge the traditional medical practice as a pioneering approach for present-day ailments. However, the study concludes that the use of KRV depends on safety dosage and genuine preparation as described by ancient saints.

High-Precision Synthesis of RNA-Loaded Lipid Nanoparticles for Biomedical Applications.

The recent development of RNA-based therapeutics in delivering nucleic acids for gene editing and regulating protein translation has led to the effective treatment of various diseases including cancer, inflammatory and genetic disorder, as well as infectious diseases. Among these, lipid nanoparticles (LNP) have emerged as a promising platform for RNA delivery and have shed light by resolving the inherent instability issues of naked RNA and thereby enhancing the therapeutic potency. These LNP consisting of ionizable lipid, helper lipid, cholesterol, and poly(ethylene glycol)-anchored lipid can stably enclose RNA and help them release into the cells' cytosol. Herein, the significant progress made in LNP research starting from the LNP constituents, formulation, and their diverse applications is summarized first. Moreover, the microfluidic methodologies which allow precise assembly of these newly developed constituents to achieve LNP with controllable composition and size, high encapsulation efficiency as well as scalable production are highlighted. Furthermore, a short discussion on current challenges as well as an outlook will be given on emerging approaches to resolving these issues.

Plasmonic Scattering Imaging of Surface-Bonded Nanoparticles at the Solution-Solid Interface.

Imaging nanoscale objects at interfaces is essential for revealing surface-tuned mechanisms in chemistry, physics, and life science. Plasmonic-based imaging, a label-free and surface-sensitive technique, has been widely used for studying the chemical and biological behavior of nanoscale objects at interfaces. However, direct imaging of surface-bonded nanoscale objects remains challenging due to uneven image backgrounds. Here, we present a new surface-bonded nanoscale object detection microscopy that eliminates strong background interference by reconstructing accurate scattering patterns at different positions. Our method effectively functions at low signal-to-background ratios, allowing for optical scattering detection of surface-bonded polystyrene nanoparticles and severe acute respiratory syndrome coronavirus 2 pseudovirus. It is also compatible with other imaging configurations, such as bright-field imaging. This technique complements existing methods for dynamic scattering imaging and broadens the applications of plasmonic imaging techniques for high-throughput sensing of surface-bonded nanoscale objects, enhancing our understanding of the properties, composition, and morphology of nanoparticles and surfaces at the nanoscale.

Recent Trends in Lateral Flow Immunoassays with Optical Nanoparticles.

Rapid, accurate, and convenient diagnosis is essential for effective disease management. Various detection methods, such as enzyme-linked immunosorbent assay, have been extensively used, with lateral flow immunoassay (LFIA) recently emerging as a major diagnostic tool. Nanoparticles (NPs) with characteristic optical properties are used as probes for LFIA, and researchers have presented various types of optical NPs with modified optical properties. Herein, we review the literature on LFIA with optical NPs for the detection of specific targets in the context of diagnostics.

Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Development of Nanopackaging for Storage and Transport of Loaded Lipid Nanoparticles.

Easily deploying new vaccines globally to combat disease outbreaks has been highlighted as a major necessity by the World Health Organization. RNA-based vaccines using lipid nanoparticles (LNPs) as a drug delivery system were employed to great effect during the recent COVID-19 pandemic. However, LNPs are still unstable at room temperature and agglomerate over time during storage, rendering them ineffective for intracellular delivery. We demonstrate the suitability of nanohole arrays (nanopackaging) as patterned surfaces to separate and store functionalized LNPs (fLNPs) in individual recesses, which can be expanded to other therapeutics. Encapsulating calcein as a model drug, we show through confocal microscopy the effective loading of fLNPs into our nanopackaging for both wet and dry systems. We prove quantifiably pH-mediated capture and subsequent unloading of over 30% of the fLNPs using QCM-D on alumina surfaces altering the pH from 5.5 to 7, displaying controllable storage at the nanoscale.

Evidence of Copper Nanoparticles and Poly I:C Modulating Cas9 Interaction and Cleavage of COR (Conserved Omicron RNA).

Conserved omicron RNA (COR) is a 40 base long 99.9% conserved sequence in SARS-CoV-2 Omicron variant, predicted to form a stable stem loop, the targeted cleavage of which can be an ideal next step in controlling the spread of variants. The Cas9 enzyme has been traditionally utilized for gene editing and DNA cleavage. Previously Cas9 has been shown to be capable of RNA editing under certain conditions. Here we investigated the ability of Cas9 to bind to single-stranded conserved omicron RNA (COR) and examined the effect of copper nanoparticles (Cu NPs) and/or polyinosinic-polycytidilic acid (poly I:C) on the RNA cleavage ability of Cas9. The interaction of the Cas9 enzyme and COR with Cu NPs was shown by dynamic light scattering (DLS) and zeta potential measurements and was confirmed by two-dimensional fluorescence difference spectroscopy (2-D FDS). The interaction with and enhanced cleavage of COR by Cas9 in the presence of Cu NPs and poly I:C was shown by agarose gel electrophoresis. These data suggest that Cas9-mediated RNA cleavage may be potentiated at the nanoscale level in the presence of nanoparticles and a secondary RNA component. Further explorations in vitro and in vivo may contribute to the development of a better cellular delivery platform for Cas9.

Updates on the Biofunctionalization of Gold Nanoparticles for the Rapid and Sensitive Multiplatform Diagnosis of SARS-CoV-2 Virus and Its Proteins: From Computational Models to Validation in Human Samples.

Since the outbreak of the pandemic respiratory virus SARS-CoV-2 (COVID-19), academic communities and governments/private companies have used several detection techniques based on gold nanoparticles (AuNPs). In this emergency context, colloidal AuNPs are highly valuable easy-to-synthesize biocompatible materials that can be used for different functionalization strategies and rapid viral immunodiagnosis. In this review, the latest multidisciplinary developments in the bioconjugation of AuNPs for the detection of SARS-CoV-2 virus and its proteins in (spiked) real samples are discussed for the first time, with reference to the optimal parameters provided by three approaches: one theoretical, via computational prediction, and two experimental, using dry and wet chemistry based on single/multistep protocols. Overall, to achieve high specificity and low detection limits for the target viral biomolecules, optimal running buffers for bioreagent dilutions and nanostructure washes should be validated before conducting optical, electrochemical, and acoustic biosensing investigations. Indeed, there is plenty of room for improvement in using gold nanomaterials as stable platforms for ultrasensitive and simultaneous "in vitro" detection by the untrained public of the whole SARS-CoV-2 virus, its proteins, and specific developed IgA/IgM/IgG antibodies (Ab) in bodily fluids. Hence, the lateral flow assay (LFA) approach is a quick and judicious solution to combating the pandemic. In this context, the author classifies LFAs according to four generations to guide readers in the future development of multifunctional biosensing platforms. Undoubtedly, the LFA kit market will continue to improve, adapting researchers' multidetection platforms for smartphones with easy-to-analyze results, and establishing user-friendly tools for more effective preventive and medical treatments.

Use of stimulatory responsive soft nanoparticles for intracellular drug delivery.

Drug delivery has made tremendous advances in the last decade. Targeted therapies are increasingly common, with intracellular delivery highly impactful and sought after. Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles. One way this can be addressed is through using stimuli-responsive soft nanoparticles, which contain materials with an organic backbone such as lipids and polymers. The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli. The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired. Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles. Internal stimuli include pH, oxidation, and enzymes, while external stimuli include ultrasound, light, electricity, and magnetic fields. Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

A Novel SPR Immunosensor Based on Dual Signal Amplification Strategy for Detection of SARS-CoV-2 Nucleocapsid Protein.

Since the global outbreak of coronavirus disease 2019 (COVID-19), it has spread rapidly around the world. The nucleocapsid (N) protein is one of the most abundant SARS-CoV-2 proteins. Therefore, a sensitive and effective detection method for SARS-CoV-2 N protein is the focus of research. Here, we developed a surface plasmon resonance (SPR) biosensor based on the dual signal-amplification strategy of Au@Ag@Au nanoparticles (NPs) and graphene oxide (GO). Additionally, a sandwich immunoassay was utilized to sensitively and efficiently detect SARS-CoV-2 N protein. On the one hand, Au@Ag@Au NPs have a high refractive index and the capability to electromagnetically couple with the plasma waves propagating on the surface of gold film, which are harnessed for amplifying the SPR response signal. On the other hand, GO, which has the large specific surface area and the abundant oxygen-containing functional groups, could provide unique light absorption bands that can enhance plasmonic coupling to further amplify the SPR response signal. The proposed biosensor could efficiently detect SARS-CoV-2 N protein for 15 min and the detection limit for SARS-CoV-2 N protein was 0.083 ng/mL, with a linear range of 0.1 ng/mL~1000 ng/mL. This novel method can meet the analytical requirements of artificial saliva simulated samples, and the developed biosensor had a good anti-interference capability.

Cerium Oxide Nanoparticles/Polyacrylonitrile Nanofibers as Impervious Barrier against Viral Infections.

BACKGROUND: Using face masks is one of the protective measures to reduce the transmission rate of coronavirus. Its massive spread necessitates developing safe and effective antiviral masks (filters) applying nanotechnology. METHODS: Novel electrospun composites were fabricated by incorporating cerium oxide nanoparticles (CeO2 NPs) into polyacrylonitrile (PAN) electrospun nanofibers that can be used in the future in face masks. The effects of the polymer concentration, applied voltage, and feeding rate during the electrospinning were studied. The electrospun nanofibers were characterized using SEM, XRD, FTIR, and tensile strength testing. The cytotoxic effect of the nanofibers was evaluated in the Vero cell line using the MTT colorimetric assay, and the antiviral activity of the proposed nanofibers was evaluated against the human adenovirus type 5 (ADV-5) respiratory virus. RESULTS: The optimum formulation was fabricated with a PAN concentration of 8%, w/v loaded with 0.25%, w/v CeO2 NPs with a feeding rate of 26 KV and an applied voltage of 0.5 mL/h. They showed a particle size of 15.8 ± 1.91 nm and a zeta potential of -14 ± 0.141 mV. SEM imaging demonstrated the nanoscale features of the nanofibers even after incorporating CeO2 NPs. The cellular viability study showed the safety of the PAN nanofibers. Incorporating CeO2 NPs into these fibers further increased their cellular viability. Moreover, the assembled filter could prevent viral entry into the host cells as well as prevent their replication inside the cells via adsorption and virucidal antiviral mechanisms. CONCLUSIONS: The developed cerium oxide nanoparticles/polyacrylonitrile nanofibers can be considered a promising antiviral filter that can be used to halt virus spread.

Bright photon upconversion in LiYbF4:Tm3+@LiYF4 nanoparticles and their application for singlet oxygen generation and in immunoassay for SARS-CoV-2 nucleoprotein.

Photon upconversion is an intensively investigated phenomenon in the materials sciences due to its unique applications, mainly in biomedicine for disease prevention and treatment. This study reports the synthesis and properties of tetragonal LiYbF4:Tm3+@LiYF4 core@shell nanoparticles (NPs) and their applications. The NPs had sizes ranging from 18.5 to 23.7 nm. As a result of the energy transfer between Yb3+ and Tm3+ ions, the synthesized NPs show intense emission in the ultraviolet (UV) range up to 347 nm under 975 nm excitation. The bright emission in the UV range allows for singlet oxygen generation in the presence of hematoporphyrin on the surface of NPs. Our studies show that irradiation with a 975 nm laser of the functionalized NPs allows for the production of amounts of singlet oxygen easily detectable by Singlet Oxygen Sensor Green. The high emission intensity of NPs at 800 nm allowed the application of the synthesized NPs in an upconversion-linked immunosorbent assay (ULISA) for highly sensitive detection of the nucleoprotein from SARS-CoV-2, the causative agent of Covid-19. This article proves that LiYbF4:Tm3+@LiYF4 core@shell nanoparticles can be perfect alternatives for the most commonly studied upconverting NPs based on the NaYF4 host compound and are good candidates for biomedical applications.

Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

Building Up to a Bright Future

Dissolution testing is an integral part of pharmaceutical development, providing drug companies with the analytical ability to determine the efficacy, bioequivalence, and bioavailability of the active drug substance, as well as control quality, stability, and consistency of the final drug product. [...]there is also a shift in focus to more novel and personalized dosage forms that is happening within the bio/pharma industry, requiring modifications to many different areas of drug development and manufacturing, including dissolution testing, Spisak added. Novel formulations can pose challenges when using standard apparatus;nanoparticles, for example, are not necessarily sufficiently separated from the dissolution medium with standard techniques. [...]modification of the instrumentation, such as that found in Agilent's NanoDis system, is required to ensure an accurate prediction of in-vivo performance of the drug product can be made.

Considering Bio/Pharma Reformulation Strategies

[...]of the significant cost of development, companies seek to recoup finances through data exclusivity and patent protection of intellectual property, such as the drug product's formulation. Bio/pharma companies reformulate existing therapies for a whole host of reasons, such as treating underserved or neglected disease areas, improving patient adherence (particularly for target patient groups, such as paediatrics), reducing the potential of drug abuse, and providing alternative options in crisis situations-as has been apparent during the COVID-19 pandemic. Pentamidine is an anti-infective agent that can be used to treat an earlier stage of the disease;however, it is unable to penetrate the blood-brain barrier sufficiently to treat the secondary stage of HAT. [...]it was hypothesized that a combined pentamidine-Pluronic formulation may be a suitable approach to provide patients with a single therapeutic option for treatment of all stages of HAT. [...]it was concluded that the pharmacokinetic data attained supports the use of safety and tolerability data from the conventional risperidone formulation for further testing of VAL401 (4).

A new strategy to integrate silver nanowires with waterborne coating to improve their antimicrobial and antiviral properties

PurposeThis study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own.Design/methodology/approachPrepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated.FindingsThe obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses.Originality/valueThe new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

Beyond Lyophilization

The company's Lyoguard trays are being used in the production of mAbs;diagnostics tests for COVID-19 virus or antibodies;and some of the key raw materials used in messenger RNA (mRNA) vaccines, including synthetic oligonucleotides, adjuvants, and lipid nanoparticles, he says. [...]it's a question of capacity. Another problem is the fact that lyophilization involves very slow cooling, at a rate of one degree Kelvin per second, says Bill Williams, a professor at the University of Texas and inventor of the thin-film freezing process, which he developed years ago at the Dow Chemical Co. TFF Pharma licensed his technology and commercialized it in 2019. Williams and his team, with corporate and US government funding, are now focusing on research designed to optimize use of thin-film freezing to improve the processing and delivery of biologics, including vaccines, along with the cold chain.

Nanoparticles as an exotic antibacterial, antifungal, and antiviral agents

Globally, concerns regarding the COVID-19 pandemic its prevention have become important. Because of COVID-19 and other microbial diseases, enhance research work has emerged revealing new antimicrobial and antiviral materials and techniques. Tremendous growth in nanotechnology has opened up the door to fabricating numerous nanomaterials. These nanomaterials are employed as antimicrobial and antiviral agents for various applications with 99.99% effectiveness compared with conventional techniques. Nanoparticles possess unique physicochemical characteristics for multiple applications. This chapter details the use of nanoparticles for antifungal, antimicrobial, and antiviral applications. It describes various kinds of nanoparticles, such as nanometals, metal oxides, polymeric nanomaterials, and carbon-based nanomaterials. © 2023 Elsevier Inc. All rights reserved.

Tangerine (Citrus reticulata L.) Wastes: Chemistry, Properties and Applications

Horticultural crops, especially fruits and vegetables, are highly consumed as food and food products. These items are consumed either uncooked, partially cooked, or fully cooked, according to their nature and the cooking process. A large amount of waste is generated from fruit-and vegetable-based industries and household kitchens. According to the FAO, waste generated from fruits and vegetable processing is estimated by 25–30% of the total product. This waste is rich in active compounds and has high nutritional content. Utilization of this waste into beneficial by-products could represent an essential strategy for reducing significant dietary and economic loss as well as the negative environmental impacts. The most common wastes include pomace, peels, rind, and seeds are fabulously rich in valuable bioactive compounds such as carotenoids, enzymes, phenolics, essential oils, vitamins, and many other compounds. These bioactive compounds show their application in various industries, including food industries to develop edible films, health industries for probiotics, and other industries for valuable and natural products. The utilization of these low-cost waste for producing the high value-added product is a novel step in its sustainable utilization. Tangerine is commonly produced and consumed as fresh or processed worldwide. The Mediterranean area produces the best and high-quality tangerine in the world. It is a high vitamin C source and rich in nutrients and provides many medicinal and health benefits. According to the new information released by the FAO, considering the influences of the novel coronavirus (COVID-19), populations with extreme starvation in the world will perhaps increase. Consequently, countries should gain proficiencies and try to reduce trade-related costs, for example, by reducing food waste and losses. Therefore, the present chapter intends to summarize the different types of waste originating from Tangerine (Citrus reticula L.) and highlight their potential in developing edible films, probiotics, nanoparticles, carbon dots, microbial media, biochar, and biosorbents. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Meeting Fill/Finish Challenges for COVID-19 Vaccines

"Lyophilization may be necessary to decrease prohibitive storage temperature requirements, allowing for shipment and storage in areas of the world where refrigeration isn't as easily accessed. "The challenge posed by the COVID-19 vaccines at the fill/finish stage of manufacturing stems from the fact that these candidates are dispersions," adds Eatmon, who explains that the dispersion factor makes the vaccines sensitive to shear stress because they are a lipid nanoparticle rather than a solution. [...]the manufacturer or CDMO/ CMO must pay close attention to foaming during liquid formulation filling and must reduce the rate of vial filling to accommodate excipients that foam, she notes. Other than the API, excipients sometimes include: antibiotics, to prevent contamination by bacteria;adjuvants that help stimulate a stronger immune response;and stabilizers, to keep the vaccine potent during transportation and storage," he notes, further explaining that the types of API used all help to ensure the product's stability, and that each type plays a different role while in storage. cdmo/cmo readiness Fill/finish operations are predominantly outsourced to CDMOs/CMOs, which are well suited to handle COVID-19 vaccines as these products start to hit the market.