Imidazolium-Based Ionic Liquid-Assisted Silver Nanoparticles and Their Antibacterial Activity: Experimental and Density Functional Theory Studies.

The exclusive properties of ionic liquids (ILs) offer various opportunities to develop advanced materials with appreciable therapeutic applications. Imidazolium-based ILs have been frequently used as reaction media and stabilizers for the development and surface functionalization of noble metal nanoparticles (NPs). This study reports the citrate-mediated reduction of silver ions in three different ILs, that is, 1-ethyl-3-methylimidazolium methyl sulfate ([EMIM][MS]), 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([BMIM][OTf]), and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][TFSI]). The resulting Ag-ILs NPs were characterized using many analytical techniques, including UV-visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction (XRD). DLS and XRD characterization revealed the negatively charged Ag-[EMIM][MS] NPs, Ag-[BMIM][OTf] NPs, and Ag-[BMIM][TFSI] NPs with mean hydrodynamic sizes of 278, 316, and 279 nm, respectively, and a face-centered cubic structure. These hybrid nanomaterials were subjected to in vitro antibacterial screening against three bacterial strains. The Ag-[BMIM][OTf] NPs exhibited significant activities against Escherichia coli, Staphylococcus aureus, and Enterobacter cloacae. The lowest inhibition concentration of 62.5 µg/mL was recorded against E. coli using Ag-[EMIM][MS] and Ag-[BMIM][OTf] NPs. Further, the density functional theory calculations carried out on the computed Ag-ILs in the gas phase and water showed relatively stable systems. Ag-[BMIM][TFSI] exhibited the lowest Gibbs free energy change of -34.41 kcal/mol. The value of the global electrophilicity index (ω = 0.1865 eV) for the Ag-[BMIM][OTf] correlated with its good antibacterial activity.

Zn nutrients-loaded chitosan nanocomposites and their efficacy as nanopriming agents for maize (Zea mays) seeds.

Recent breakthroughs in agro-inputs research have led to the development of nanomaterials that can promote precision agriculture and better environmental security. The agricultural sector is increasingly facing the negative impacts of changing climates due to various stress conditions. To curb this scenario, economical and low-risk practices such as decreasing fertilizer inputs and seed priming have been promoted. In the current study, the H. odoratissimum aqueous extract was used to nucleate the Zn ionic species and grow the zinc oxide nanoparticles (ZnO NPs). The developed nanocomposites and their ionic zinc precursor were then integrated into tripolyphosphate (TPP)-crosslinked chitosan (CS/TPP) nanostructures by ionic gelation. Advanced physicochemical characterization techniques (SEM, EDS, TEM, DLS, FTIR, TGA, and XPS) were exploited to report the morphology, hydrodynamic size, surface charge, and structural organization of the developed nanomaterials. These revealed positively charged particles with hydrodynamic size in the 149-257 nm range. The NPs were used as priming agents for Zea mays seeds. At 0.04%, the ZnO-loaded CS/TPP NPs achieved higher root and shoot elongation in 10-day old seedlings compared to other treatments. The pristine CS/TPP NPs, Zn(II)-laden CS/TPP NPs, and ZnO-loaded CS/TPP NPs at 0.01% significantly promoted the early seedling development of seeds under salt stress. This represents the first report showing ZnO integrated chitosan nanocomposites as an auspicious nanopriming agent for stimulating the seed germination of maize. The study envisages offering perspectives on utilizing green nanotechnology to improve the early seedling development of maize. Furthermore, it has the potential to contribute towards UN SDG 2, thus addressing the threats to global food insecurity and doubling agricultural productivity by 2030.

Next-Generation Vaccines: Nanovaccines in the Fight against SARS-CoV-2 Virus and beyond SARS-CoV-2.

The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.

Green Synthesis of Characterized Silver Nanoparticle Using Cullen tomentosum and Assessment of Its Antibacterial Activity.

Plants serve as an important source of medicine and provide suitable candidate compounds to produce eco-friendly therapeutic agents. They also represent a source of bio-reducer and stabilizer for the development of nanoparticles for downstream applications. This study focused on the green synthesis of silver nanoparticle (CTAgNP) using Cullen tomentosum (Thunb.) J.W. Grimes acetone extract and the evaluation of the antibacterial activity of the plant extract and biogenic nanoparticles against two Gram-positive bacteria strains, namely Bacillus cereus and Staphylococcus aureus. In addition, the phytochemical profile of C. tomentosum was established using liquid chromatography-mass spectrometry (LC-MS). The antibacterial effect of the extract and CTAgNP was moderate based on the minimum inhibitory concentration (MIC) values obtained. The MIC values of 2.6 mg/mL and 3.1 mg/mL were recorded for C. tomentosum extract against B. cereus and S. aureus, respectively. On the other hand, the CTAgNP had MIC values of 1.5 mg/mL and 2.6 mg/mL against B. cereus and S. aureus, respectively. The nanoparticle exhibited surface charge of -37 ± 7.67 mV and average hydro-dynamic size of 145 nm. X-ray diffraction illustrates that metallic nanoparticles were formed and had a face-centered cubic structure. Microscopic and spectroscopic techniques revealed that the CTAgNP was covered by a protective shell layer constituted of organic compounds originating from the plant extract. The acetone extract of C. tomentosum could be useful to the bio-pharma industries in the large-scale manufacture of nanoparticle-based medications to fight against microbes that constitute a threat to the survival of humanity.

Protective Roles and Mechanism of Action of Plant Flavonoids against Hepatic Impairment: Recent Developments.

BACKGROUND: The liver is one of the crucial organs in humans and is responsible for the regulation of diverse processes, including metabolism, secretion, and detoxification. Ingestion of alcohol and drugs, environmental pollutants, and irradiation are among the risk factors accountable for oxidative stress in the liver. Plant flavonoids have the potential to protect the liver from damage caused by a variety of chemicals. OBJECTIVE: The present study aims to summarize up-to-date information on the protective roles of plant flavonoids against liver damage. METHODOLOGY: The literature information on the hepatoprotective plant flavonoids was assessed through various databases, which were searched from their respective inception until March 2022. RESULTS: More than 70 flavonoids with hepatoprotective activity against a variety of models of liver toxicity have been reported across the literature. Among these are flavones (19), flavonols (30), flavanones (9), isoflavonoids (5), and biflavonoids (2). Several hepatoprotective mechanisms of action were reported in various classes of flavonoids, including flavones and flavonols (upregulation of the pro-survival ERK1/2 pathway; downregulation of apoptotic proteins, including Bax, Bcl-2, Bax, BH3, caspase-3, 8, 9, etc.), flavanones (downregulation of NF-κB, TNF-α, IL-1 ß, IL-6, iNOS, etc.), isoflavonoids (downregulation of lipogenesis genes, such as SREBP-1c, LXRα, RXRα, PPARγ and ACC2, with concomitant upregulation of genes involved in ß-oxidation, including AMPK and PPARα; inhibition of CYPs, such as CYP1A1, CYP1A2, CYP2B1, CYP2D6, CYP2E1 and CYP3A1/2). CONCLUSION: The present work demonstrated the effectiveness of plant flavonoids against hepatic damage. However, more studies need to be performed regarding the cytotoxicity, pharmacokinetics, and mechanisms of action of these very important cytoprotective flavonoids.

Triazole-containing Heterocycles: Privileged Scaffolds in Anti-Trypanosoma Cruzi Drug Development.

BACKGROUND: Chagas disease is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi and is transmitted to humans through the excreta of infected blood-sucking triatomine bugs. According to the World Health Organization, 6 to 7 million people are infected with T. cruzi worldwide, mainly in Latin America, with more than 10000 deaths annually. AIM OF THE STUDY: The present study aims to provide comprehensive literature information on the importance of triazole-containing heterocycles in developing anti-Chagas disease agents. METHODOLOGY: The embodied information was acquired without date limitation by December 2020 using various electronic databases including, SciFinder, PubMed (National Library of Medicine), Science Direct, Wiley, ACS (American Chemical Society), SciELO (Scientific Electronic Library Online), Google Scholar, Springer, Scopus, and Web of Science. RESULTS: Upon in vitro studies, more than 100 triazole-containing heterocycles have been predicted as active compounds against the pathogen responsible for the American trypanosomiasis. However, less is known about their in vivo activity in animal models and their clinical studies in humans. Moreover, the pharmacokinetic studies of these bioactive compounds are still pending. Despite the variety of mechanisms of action attributed to most of these molecules, the exact mechanism involved is still controversial. Thus, in vivo experiments, followed by pharmacokinetics, and the mechanism of action of the most active compounds, should be the subject of future investigation. CONCLUSION: All in all, recent studies have demonstrated the importance of triazole-containing heterocycles in search of potential candidates for drug development against Chagas disease. Nonetheless, the use of new catalysts and chemical transformations is expected to provide avenues for the synthesis of unexplored triazole derivatives, leading to the development of triazole-containing compounds with new properties and trypanocidal activity.

In Situ Stabilisation of Silver Nanoparticles at Chitosan-Functionalised Graphene Oxide for Reduction of 2,4-Dinitrophenol in Water.

This investigation reports the in situ growth of silver nanoparticles onto covalently bonded graphene oxide-chitosan, which serve as supported nanocatalysts for the NaBH4 reduction of 2,4-dinitrophenol in aqueous systems. Fumaryl chloride reacted with chitosan in an acidic environment to yield a tailored polymeric material. The latter was, in turn, treated with the pre-synthesised graphene oxide sheets under acidic conditions to generate the GO-functionalised membrane (GO-FL-CS). The adsorption of Ag+ from aqueous media by GO-FL-CS yielded a set of membranes that were decorated with silver nanoparticles (Ag NPs@GO-FL-CS) without any reducing agent. Various analytical tools were used to characterise these composites, including Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area analysis, X-ray diffraction, scanning electron microscopy/energy-dispersive X-ray analysis, inductively coupled plasma-mass spectrometry, and transmission electron microscopy. The silver-loaded materials were further used for the remediation of 2,4-dinitrophenol from aqueous solutions under batch operation. The BET analysis revealed that the functionalisation of GO with chitosan and Ag NPs (average size 20-60 nm) resulted in a three-fold increased surface area. The optimised catalyst (Ag mass loading 16.95%) displayed remarkable activity with an apparent pseudo-first-order rate constant of 13.5 × 10-3 min-1. The cyclic voltammetry experiment was conducted to determine the nitro-conversion pathway. The reusability/stability test showed no significant reduction efficiency of this metal-laden composite over six cycles. Findings from the study revealed that Ag NPs@GO-FL-CS could be employed as a low-cost and recyclable catalyst to convert toxic nitroaromatics in wastewater.

Synergistic broad-spectrum antibacterial activity of Hypoxis hemerocallidea-derived silver nanoparticles and streptomycin against respiratory pathobionts.

Respiratory tract infections arise due to the introduction of microbes into the airway, disrupting the normal, healthy, complex interdependent microbiome. The selective disruption of this community can be either beneficial or dangerous. Nanoparticles are a potential tool for modifying this population. Coated silver nanoparticles (AgNPs) were synthesized using ethanolic extracts of Hypoxis hemerocallidea (EEHH), a Southern African plant used extensively in traditional medicine and the source of many bioactive secondary metabolites. The room temperature reaction between silver nitrate and EEHH forms largely spherical AgNPs with an average diameter of 6-20 nm. These nanoparticles show similar levels of antibacterial activity as the broad-spectrum antibiotic streptomycin against Bacillus cereus, Streptococcus pneumonia, Escherichia coli, Pseudomonas aeuroginosa, and Moraxella catarrhalis. However, the AgNPs synergistically increase the antibacterial activity of streptomycin when they are applied in combination (30-52%). AgNPs are reiterated to be promising dual-function antibiotics, synergistically enhancing activity while also acting as delivery agents for small molecules.

Applications of Nanoparticles for Herpes Simplex Virus (HSV) and Human Immunodeficiency Virus (HIV) Treatment.

Human Immunodeficiency Virus (HIV) is a global pandemic that has contributed to the burden of disease, and the synergistic interaction between Herpes Simplex Virus (HSV) and HIV has assisted further in the spread of the HIV disease. Moreover, several chemotherapeutic treatment options from antiviral monotherapy to highly active antiretroviral therapy (HAART) have been adopted to manage the infection; however, HIV has developed new mechanisms against these active pharmaceutical agents (APAs), limiting the effect of the drugs. In this article, we reviewed different nanoparticles and their antiviral potency against HSV and HIV infection as well as the effect of drug encapsulated nanoparticles using different drug delivery systems as they palliate to some flaws or deficiencies that the stand-alone drugs present. Drug encapsulated nanoparticles show better treatment outcomes of HSV and HIV infection. The nanoparticles can transverse the anatomic privilege sites to exert their therapeutic effect, and a prolonged and higher dose of the encapsulated therapeutic agent can ease the dosage frequency, thus palliating low drug compliance which the stand-alone drugs fail to perform. Therefore, it is clear that nanoparticles prevent antiviral drug resistance by maintaining sustained drug release over an extended period, improving the therapeutic effect of the entrapped drug

Integrated genome-based probiotic relevance and safety evaluation of Lactobacillus reuteri PNW1.

This study evaluates whole-genome sequence of Lactobacillus reuteri PNW1 and identifies its safety genes that may qualify it as a putative probiotic. It further extracted the bacteriocin produced by the strain and tested its effectiveness against pathogenic STEC E. coli O177. The genomic DNA was sequenced on illuminal Miseq instrument and the sequenced data was assessed for quality reads before assembled with SPAdes. The draft assembly was annotated with Prokaryotic Genome Annotation Pipeline (PGAP) and Rapid Annotations using Subsystems Technology (RAST). Further downstream analyses were carried out using appropriate bioinformatic tools. Production of biogenic amines was biochemically confirmed through HPLC analysis. The assembled genome was 2,430,215 bp long in 420 contigs with 39% G+C content. Among all known genes, putatively responsible for the production of toxic biochemicals, only arginine deiminase (EC3.5.3.6) was spotted. Coding sequences (CDS) putative for D-lactate dehydrogenase (EC1.1.1.28), L-lactate dehydrogenase (EC1.1.1.27) and bacteriocin helveticin J were found within the genome together with plethora of other probiotic important genes. The strain harbours only resistant genes putative for Lincosamide (lnuC) and Tetracycline resistant genes (tetW). There was no hit found for virulence factors and probability of the strain being a human pathogen was zero. Two intact prophage regions were detected within the genome of L. reuteri PNW1 and nine CDS were identified for insertion sequence by OASIS which are belong to seven different families. Five putative CDS were identified for the CRISPR, each associated with Cas genes. Maximum zone of inhibition exhibited by the bacteriocin produced L. reuteri PNW1 is 20.0±1.00 mm (crude) and 23.3±1.15 mm (at 0.25 mg/ml) after being partially purified. With the strain predicted as non-human pathogen, coupled with many other identified desired features, L. reuteri PNW1 stands a chance of making good and safe candidates for probiotic, though further in-vivo investigations are still necessary.

Polyethylene glycol (5,000) succinate conjugate of lopinavir and its associated toxicity using Danio rerio as a model organism.

Lopinavir (LPV), a well-known drug administered in human immunodeficiency virus (HIV) infection, has shown limitation for pediatric treatment owing to poor aqueous solubility that gives rise to limited oral bioavailability and short plasma half-life (5-6 h). Polymers such as polyethylene glycol (PEG) have been used as drug carriers to improve their solubility. This study reports the preparation of polyethylene glycol (5,000) succinate (PEG-Suc-LPV) conjugate of LPV by the esterification method. The disappearance of the 3,395 cm-1 (O-H stretch of COOH) band for Polyethylene glycol (5,000) succinate (PEG-Suc )confirms the formation ester linkage with the OH group of LPV which is also confirmed by 1H NMR analysis. The XRD for the conjugate showed a broad, amorphous peak while pure PEG, Suc, LPV are crystalline. DSC analysis showed that the conjugate exhibited new broad and diffuse peaks, confirming that they did exist in an amorphous state as multiple complexes. The conjugate showed improved solubility and activity with reduced toxicity compared to pure LPV. The solubility of LPV increased significantly from 80 to 318 ppm. Furthermore, an aquatic toxicity test using Danio rerio showed that the conjugate had a lower LC50 (60.8 ppm) when compared to the pure LPV drug LC50 (6.42 ppm). These results suggest PEG-Suc conjugate of LPV as an efficient carrier for enhanced hydrophilicity and anti-HIV property of LPV.

Nanoformulated Eudragit lopinavir and preliminary release of its loaded suppositories.

The development of novel paediatrics formulations is critical towards achieving the UNAIDS 90-90-90 targets. According to the latest UNAIDS reports, the availability of antiretrovirals (ARVs) for children has increased significantly, from 49% in 2015 to 53% in 2017. However, this percentage is considerably lower than the 80% for pregnant women that are currently on treatment. Therefore, there is still an urgent need for an alternative child-friendly delivery system. Lopinavir (LPV) is a protease inhibitor first-line HIV treatment drugs but suffers from low aqueous solubility, bitter state, short half-life leading to a limited dissolution and variable bioavailability upon oral administration. This work focused on the fabrication and characterization of a delivery system entailing Eudragit RSPO-LPV nanoparticles loaded suppositories in two different bases to improve the bioavailability and overcome the problem encountered through oral administration emanating from poor solubility. The prepared nanoparticles by nanoprecipitation method were characterized and compounded into suppositories in fattibase and polyethylene glycol (PEG) bases using a melt fusion method. The suppositories were stored at 5 and 25 °C, and were sampled at 0, 4, 8, 12 weeks. The samples were assessed by particle size, entrapment efficiency (EE), zeta potential and polydispersity index (PDI) variations. The preliminary in vitro release studies were analysed by HPLC. The nanoparticles have an average particle size of 191 nm with spherical morphology, entrapment efficiency, polydispersity index and zeta potential of 79.0 ± 0.5%, 0.224, and 25.87 ± 0.41 mV respectively. The surface analysis of the nanoparticles with FTIR, SEM, PXRD and TGA indicated that the drug was truly encapsulated without any interaction. The in vitro release studies showed that a better release was observed in suppositories formulated with PEG than the fattibase by having higher drug concentration released. Hence, this rectal formulation might serve as an alternative for paediatric HIV treatment upon further investigation.

Influence of Magnetic Nanoparticles on Modified Polypyrrole/m-Phenylediamine for Adsorption of Cr(VI) from Aqueous Solution.

A novel, modified polypyrrole/m-phenylediamine (PPy-mPD) composite, decorated with magnetite (Fe3O4) nanoparticles, and prepared via an in-situ oxidative polymerisation, was investigated. The PPy-mPD/Fe3O4 nanocomposite was employed for the removal of highly toxic oxyanion hexavalent chromium Cr(VI) from an aqueous solution. The structure and successful formation of the PPy-mPD/Fe3O4 nanocomposite was confirmed and investigated using various techniques. The presence of Fe3O4 was confirmed by high resolution transmission electron microscopy, with an appearance of Fe lattice fringes. The estimation of the saturation magnetisation of the nanocomposite, using a vibrating sample magnetometer, was observed to be 6.6 emu/g. In batch adsorption experiments, PPy-mPD/Fe3O4 nanocomposite (25 mg) was able to remove 99.6% of 100 mg/L of Cr(VI) at pH 2 and 25 °C. Adsorption isotherms were investigated at different Cr(VI) concentration (100-600 mg/L) and temperature (15-45 °C). It was deduced that adsorption follows the Langmuir model, with a maximum adsorption capacity of 555.6 mg/g for Cr(VI) removal. Furthermore, isotherm data were used to calculate thermodynamic values for Gibbs free energy, enthalpy change and entropy change, which indicated that Cr(VI) adsorption was spontaneous and endothermic in nature. Adsorption-desorption experiments revealed that the nanocomposite was usable for two consecutive cycles with no significant loss of adsorption capacity. This research demonstrates the application potential for the fascinating properties of PPy-mPD/Fe3O4 nanocomposite as a highly efficient adsorbent for the removal of heavy metal ions from industrial wastewater.