Exposure Assessment of Essential and Potentially Toxic Metals in Wheat-Based Sweets for Human Consumption: Multivariate Analysis and Risk Evaluation Studies.

In recent years, there has been a growing concern about the negative impact of unforeseen contaminants such as metals in commonly consumed food items, which pose a threat to human well-being. Therefore, it is of utmost importance to evaluate the levels of these contaminants to guarantee the safe consumption of these food items. The goal of the current research is to determine the levels of essential (EMs: Mg, Ca, Mn, Fe, Co, Cu, and Zn) and potentially toxic metals (PTMs: Al, Cr, Ni, As, Cd, and Pb) in various brands of wheat-based sweets. One hundred samples were collected and analysed via flame atomic absorption spectrometry (FAAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Also, the current study was to investigate the distribution, correlation, and multivariate analysis of 13 metals (Mg, Ca, Mn, Fe, Co, Cu, Zn, Al, Cr, Ni, As, Cd, and Pb). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to interpret the metals' association. The concentration (mg/kg) ranges of EMs were, in order, Mg (12.70-65.67), Ca (24.02-209.12), Mn (1.32-9.61), Fe (4.55-111.23), Co (0.32-8.94), Cu (2.12-8.61), and Zn (2.60-19.36), while the concentration (mg/kg) ranges of PTMs were, in order, Al (0.32-0.87), Cr (0.17-5.74), Ni (0.36-1.54), Cd (0.16-0.56), and Pb (0.14-0.92), and As was not detected in any sample under investigation. The HCA data revealed that Co, Al, and Ni form clusters with other metals. Sweets are prepared at high temperatures, and the elevated temperatures can increase the likelihood of Ni and Al leaching from stainless steel. Tolerable dietary intake (TDI) values for Ni were higher than the values established by the European Food Safety Authority (EFSA). The CR value found for the Ni and Cr was at the threshold level of cancer risk, if an amount of 25 g were to be used over a lifetime. In a nutshell, this study highlights the monitoring of EM and PTM levels in wheat-based sweets, and from a food safety perspective, the study is important for consumers of wheat-based sweets.

A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 µM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

Template-assisted synthesis of molecularly imprinted polymers for the removal of methyl red from aqueous media.

This study entails the synthesis of molecularly imprinted polymers (MIPs) with good selectivity coefficients for azo dye as a potential sorbent material to extract azo dye from polluted aqueous media. A series of MIPs for methyl red (MR) as a template, were synthesized by changing the molar ratio of functional monomers, via precipitation polymerization format of non-covalent approach. Water-soluble functional monomer; acrylic acid (AA) was used to weave the frame work of polymers while ethylene glycol dimethacrylate (EGDMA) was utilized as crosslinking monomer. The impact of different experimental parameters, such as mole ratio of monomer (functional) to crosslinking monomer on the molecular recognition was investigated. The highly efficient and selective MR-MIP was used for the removal of spiked MR dye from different water samples. The selected imprinted polymer, MR1-MIP was able to selectively remove the MR molecules from aqueous media. A significant amount of dye was removed by MR1-MIP from the river water samples with a high degree of removal efficiency i.e. 92.25%. The imprinting factor of 3.75 for MR1-MIP indicated that the high selectivity in terms of adsorption for MR. A minimum loss of only ~ 3.35% in the removal efficiency within ten sequential cycles of adsorption-desorption study evidenced that MR-MIPs could be used as the most cost effective and best sorbent for the removal of MR from polluted water. Furthermore, the structural properties of MR-MIPs were characterized by FTIR and EDX, whereas TGA, SEM and BET were used to describe the thermal, morphological and surface structures of the particles, respectively.

Metal organic frameworks as promising sensing tools for electrochemical detection of persistent heavy metal ions from water matrices: A concise review.

Water bodies are being polluted rapidly by disposal of toxic chemicals with their huge entrance into drinking water supply chain. Among these pollutants, heavy metal ions (HMIs) are the most challenging one due to their non-biodegradability, toxicity, and ability to biologically hoard in ecological systems, thus posing a foremost danger to human health. This can be addressed by robust, sensitive, selective, and reliable sensing of metal ions which can be achieved by Metal organic frameworks (MOF) based electrochemical sensors. In the present era, MOFs have caught greater interest in a variety of applications including sensing of hazardous pollutants such as heavy metal ions. So, in this review article, types, synthesis and working mechanism of MOF based sensors is explained to give general overview with updated literature. First time, detailed study is done for sensing of metal ions such as chromium, mercury, zinc, copper, manganese, palladium, lead, iron, cadmium and lanthanide by MOFs based electrochemical sensors. The use of MOFs as electrochemical sensors has attractive success story along with some challenges of the area. Considering these challenges, we attempted to highlight the milestone achieved and shortcomings along with future prospective of the MOFs for employing it in electrochemical sensing devices for HMIs. Finally, challenges and future prospects have been discussed to promote the development of MOFs-based sensors in future.

Metal-Organic Framework-Based Composites for the Detection and Monitoring of Pharmaceutical Compounds in Biological and Environmental Matrices.

The production of synthetic drugs is considered a huge milestone in the healthcare sector, transforming the overall health, aging, and lifestyle of the general population. Due to the surge in production and consumption, pharmaceutical drugs have emerged as potential environmental pollutants that are toxic with low biodegradability. Traditional chromatographic techniques in practice are time-consuming and expensive, despite good precision. Alternatively, electroanalytical techniques are recently identified to be selective, rapid, sensitive, and easier for drug detection. Metal-organic frameworks (MOFs) are known for their intrinsic porous nature, high surface area, and diversity in structural design that provides credible drug-sensing capacities. Long-term reusability and maintaining chemo-structural integrity are major challenges that are countered by ligand-metal combinations, optimization of synthetic conditions, functionalization, and direct MOFs growth over the electrode surface. Moreover, chemical instability and lower conductivities limited the mass commercialization of MOF-based materials in the fields of biosensing, imaging, drug release, therapeutics, and clinical diagnostics. This review is dedicated to analyzing the various combinations of MOFs used for electrochemical detection of pharmaceutical drugs, comprising antibiotics, analgesics, anticancer, antituberculosis, and veterinary drugs. Furthermore, the relationship between the composition, morphology and structural properties of MOFs with their detection capabilities for each drug species is elucidated.

Experimental and Computational Analysis of Newly Synthesized Benzotriazinone Sulfonamides as Alpha-Glucosidase Inhibitors.

Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, 1H-NMR and 13C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC50 values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.

Antibacterial and Wound-Healing Activities of Statistically Optimized Nitrofurazone- and Lidocaine-Loaded Silica Microspheres by the Box-Behnken Design.

In the current study, nitrofurazone- (NFZ) and lidocaine-loaded (LD) silica microspheres were fabricated to address pathological indications of skin infections. The microspheres were prepared by the sol-gel method applying the Box-Behnken design and evaluated for size distribution, morphology, zeta potential, physico-chemical compatibility, XRD, thermogravimetric analysis, antibacterial and cytotoxicity activities. The comparative in vitro drug release study of microspheres revealed a 30% release of NFZ and 33% of LD after 8 h. The microspheres showed 81% percentage yield (PY) and 71.9% entrapment efficiency. XRD patterns confirmed the entrapment of NFZ-LD in silica microspheres with a significant reduction in crystallinity of the drugs. Thermal and FTIR studies proved the absence of any profound interactions of the formulation ingredients. The smooth spherical microspheres had a -28 mV zeta potential and a 10-100 µm size distribution. In vitro antibacterial activities of the NFZ-LD microspheres showed an increased zone of inhibition compared to pure drug suspensions. The in vivo efficacy tested on rabbits showed a comparatively rapid wound healing with complete lack of skin irritation impact. The cytotoxicity studies revealed more acceptability of silica microspheres with negligible harm to cells. The study suggests that the NFZ- and LD-loaded silica microspheres would be an ideal system for accelerating and promoting rapid healing of various acute and chronic wounds.

Metal Based Bioactive Nitrogen and Oxygen Donor Mono and Bis Schiff Bases: Design, Synthesis, Spectral Characterization, Computational Analysis and Antibacterial Screening.

The scientific interest in developing the advanced metal based compounds to inhibit and control bacterial infections is continuously rising. Keeping in view their pharmacological significance, two new bioactive symmetrical phenylenediamine mono- and bis-Schiff bases, 2-{[(4-aminophenyl)imino]methyl}-6-methoxyphenol (L1) and 2,2'-{benzene-1,2-diylbis[nitrilomethylylidene]}bis(6-methoxyphenol) (L2) have been synthesized and characterized by using physical techniques, spectral methods, elemental and DFT based computational analysis with B3LYP/6-311++G(d, p) basis set. Furthermore, the synthesized ligands were complexed with VO, Mn, Co, Ni, Cu and Zn ions in ratio [M:L,1:2 and 1:1], respectively. All the complexes exhibited significant antibacterial action against all tested bacterial strains. But overall, the zinc complexes possessed higher antibacterial activity. These results concluded that metal complexes might be promising induction in the upcoming time for medical purposes.

Superporous acrylic acid and HPMC hydrogels of mefenamic acid: Formulation, characterization and optimization by central composite design.

The purpose of the study was to devise the superporous hydrogels (SPHs) of mefenamic acid (MA) to acquire the sustained action of the MA in the body. The superporous hydrogels of mefenamic acid were formulated by employing the gas blowing method. The central composite rotatable design (CCRD) was applied to optimize the effect of independent formulation factors like acrylic acid (AC), HPMC and glycerol (GLY) over dependent variables like porosity, viscosity, drug content and swelling ratio of superporous hydrogels in water, phosphate buffer (pH 6.8) and in 0.1N HCl (pH 1.2). A number of characteristics such as void fraction, surface morphology by Scanning electron microscopy (SEM) and in vitro drug release study were governed along with physico-chemical analysis by Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and appraised statistically by employing the ANOVA. The comparative analgesic activity of optimized superporous hydrogel formulation SPH17 was also analyzed by using tail flick method. The Fourier transform infrared spectroscopy and Differential scanning calorimetry studies approved the physical compatibility between the polymers and the drug. The Scanning electron microscopy study specified micrographic insight about the structure of formed formulations comprising presence of pores, fibers and drug-hole aggregates. The superporous hydrogels were detected to be low dense as they expressed density lower than 0.75 g/cc. The decrease in concentration of the polymers and cross linker contributed towards the increase in the void fraction of the superporous hydrogel formulations. The optimized formulation SPH 17 exhibited a highly sustained release of MA for up to 10 h in the both 0.1 N HCl and phosphate buffer (66.6%) media. The non-fickian release of drug revealed the coupling of the diffusion and polymer relaxation mechanism of the drug release from the formulations. The obtained outcomes suggested that analgesic effect of SPH 17 was significantly (p < 0.05) higher than that of simple suspension of mefenamic acid and total analgesic effect duration for superporous hydrogel was also doubled as compared to the duration of analgesic effect produced by drug suspension. The successfully formulated SPH with HPMC K100M as a gelling agent had sustained the action of the mefenamic acid (MF) by improving its poor solubility and permeability. The introduction of inter-penetrating polymeric network (acrylic acid) using glycerol as a cross linker impart increased residence time to superporous hydrogels which ultimately enhanced the feasibility of using superporous hydrogel as oral sustained release devices particularly for gastric retention.

Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing.

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.