Silver nanoparticle-based drug delivery systems in the fight against COVID-19: enhancing efficacy, reducing toxicity and improving drug bioavailability.

Nanoparticles (NPs) have played a pivotal role in various biomedical applications, spanning from sensing to drug delivery, imaging and anti-viral therapy. The therapeutic utilisation of NPs in clinical trials was established in the early 1990s. Silver nanoparticles (AgNPs) possess anti-microbial, anti-cancer and anti-viral properties, which make them a possible anti-viral drug to combat the COVID-19 virus. Free radicals and reactive oxygen species are produced by AgNPs, which causes apoptosis induction and prevents viral contamination. The shape and size of AgNPs can influence their interactions and biological activities. Therefore, it is recommended that silver nanoparticles (AgNPs) be used as a valuable tool in the management of COVID-19 pandemic. These nanoparticles possess strong anti-microbial properties, allowing them to penetrate and destroy microbial cells. Additionally, the toxicity level of nanoparticles depends on the administered dose, and surface modifications are necessary to reduce toxicity, preventing direct interaction between metal surfaces and cells. By utilising silver nanoparticles, drugs can be targeted to specific areas in the body. For example, in the case of COVID-19, anti-viral drugs can be stimulated as nanoparticles in the lungs to accelerate disease recovery. Nanoparticle-based systems have the capability to transport drugs and treat specific body parts. This review offers an examination of silver nanoparticle-based drug delivery systems for combatting COVID-19, with the objective of boosting the bioavailability of existing medications, decreasing their toxicity and raising their efficiency.

Photothermal performance of a novel carbon dot and its conjugate with disulfiram for prostate cancer PC3 cell therapy.

Aim: To develop and employ a copper, sulfur, nitrogen-carbon quantum dot (C,S,N-CQD) multifunctional platform for synergistic cancer therapy, combining chemotherapy and photothermal treatment with in vitro cancer cell imaging. Materials & methods: Cu,S,N-CQDs were synthesized hydrothermally, loaded with disulfiram (DSF), and characterized through UV-Vis spectrophotometry, photoluminescence, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy, dynamic light scattering, x-ray diffraction and EDAX. Results: Cu,S,N-CQD exhibited 5.5% absolute fluorescence quantum yield, 46.0% photothermal conversion efficiency and excellent stability. The release of DSF-loaded Cu,S,N-CQD, photothermal performance, and IC50 on PC3 prostate cancer cells, were evaluated. The impact of cellular glutathione on nanocarrier performance was investigated. Conclusion: Cu,S,N-CQD as a photothermal agent and DSF carrier showed synergy (combination index: 0.71) between chemotherapy and photothermal therapy. The nanocarrier simultaneously employed for in vitro cancer cell imaging due to its unique fluorescence properties.

Nanometer-scale particles can be used to treat and detect cancer in many ways. A type of nanoparticle was designed to attack cancer in two different ways. These nanoparticles ­ copper, sulfur, nitrogen­carbon quantum dots (C,S,N­CQDs) ­ were designed to both deliver a chemotherapy drug to cancer cells and act as a photothermal agent. This means that when light of a particular energy is shone on these particles, they heat up and can kill cancer cells. These C,S,N­CQDs loaded with the chemotherapy drug disulfiram were then tested on the prostate cancer cell line PC3. When a laser was shone on these particles and they became excited, they reduced cancer cell viability both by releasing the drug and heating up and killing the surrounding cells. These Cu,S,N-CQDs are also fluorescent, meaning they can be used to image cancer cells in tests like these.

A suitable drug structure for interaction with SARS-CoV-2 main protease between boceprevir, masitinib and rupintrivir; a molecular dynamics study.

In recent years, more than 200 countries of the world have faced a health crisis due to the epidemiological disease of COVID-19 caused by the SARS-CoV-2 virus. It had a huge impact on the world economy and the global health sector. Researchers are studying the design and discovery of drugs that can inhibit SARS-CoV-2. The main protease of SARS-CoV-2 is an attractive target for the study of antiviral drugs against coronavirus diseases. According to the docking results, binding energy for boceprevir, masitinib and rupintrivir with CMP are -10.80, -9.39, and -9.51 kcal/mol respectively. Also, for all investigated systems, van der Waals and electrostatic interactions are quite favorable for binding the drugs to SARS-CoV-2 coronavirus main protease, indicating confirmation of the complex stability.

Development of venetoclax performance using its new derivatives on BCL-2 protein inhibition.

Cancer cells are resistant to apoptosis and this is one of the most obvious symptoms of cancer in humans. One of the most exciting strategies for treating cancer is to design regulators that increase cell death and stop cell growth. Members of the BCL-2 family of proteins play an important role in the regulation of apoptosis. In this study, an attempt was made to improve the performance of one of the anticancer drugs by designing new analogs of venetoclax (VNT). For this purpose, molecular docking studies were performed to determine the best binding state of VNT and its newly designed derivatives at the protein-binding site to estimate the binding energy. The best analog in terms of free energy was VNT-12 with the lowest energy (-12.15 kcal/mol). Finally, to investigate the inhibitory effect of the compounds on BCL-2 protein, molecular dynamics simulation was used, and by performing the relevant analyses during the simulation, it was observed that the newly designed ligand had better performance in inhibiting BCL-2 protein compared to VNT.

Voltammetric approach for pharmaceutical samples analysis; simultaneous quantitative determination of resorcinol and hydroquinone.

A simple and precise analytical approach developed for single and simultaneous determination of resorcinol (RC) and hydroquinone (HQ) in pharmaceutical samples using carbon paste electrode (CPE) modified with 1-Ethyl-3-methylimidazolium tetrafluoroborate as ionic liquid and ZnFe2O4 nanoparticle. A significant enhancement in the peak current and sensitivity of the proposed sensor observed by using modifiers in the composition of working electrode compared to bare CPE which is in accordance with the results obtained from electrochemical impedance spectroscopy investigations. Electrochemical investigations revealed a well-defined irreversible oxidation peak for RC over a wide concentration range from 3.0 µM to 500 µM in 0.1 M phosphate buffer solution (pH 6.0) with the linear regression equations of Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.997). The limit of detection and quantification for RC analysis were found to be 1.46 µM and 4.88 µM, respectively. However, the obtained SW voltammograms for simultaneous determination of RC and HQ exhibited a desirable peak separation of about 360 mV potential difference and a satisfactory linear response over the range of 50-700 µM and 5-350 µM with the favorable correlation coefficient of 0.991 and 0.995, respectively. The diffusion coefficient (D) of RC and the electron transfer coefficient (α) at the surface of ZnFe2O4/NPs/IL/CPE estimated to be 2.83 × 10- 4 cm s- 1 and 0.76. The proposed sensor as a promising and low-cost method successfully applied for determination of RC in commercial pharmaceutical formulations such as the resorcinol cream of 2% O/W emulsion available on the market with the recovery of 98.47 ± 0.04.

Palladium-Doped Single-Walled Carbon Nanotubes as a New Adsorbent for Detecting and Trapping Volatile Organic Compounds: A First Principle Study.

Volatile organic compounds (VOCs) are in the vapor state in the atmosphere and are considered pollutants. Density functional theory (DFT) calculations with the wb97xd exchange correlation functional and the 6-311+G(d,p) basis set are carried out to explore the potential possibility of palladium-doped single-walled carbon nanotubes (Pd/SWCNT-V), serving as the resource for detecting and/or adsorbing acetonitrile (ACN), styrene (STY), and perchloroethylene (PCE) molecules as VOCs. The suggested adsorbent in this study is discussed with structural parameters, frontier molecular orbital theory, molecular electrical potential surfaces (MEPSs), natural bond orbital (NBO) analyses, and the density of states. Furthermore, following the Bader theory of atoms in molecules (AIM), the topological properties of the electron density contributions for intermolecular interactions are analyzed. The obtained results show efficient VOC loading via a strong chemisorption process with a mean adsorption energy of -0.94, -1.27, and -0.54 eV for ACN, STY, and PCE, respectively. Our results show that the Pd/SWCNT-V can be considered a good candidate for VOC removal from the environment.

In silico evaluation of atazanavir as a potential HIV main protease inhibitor and its comparison with new designed analogs.

Starting three decades ago and spreading rapidly around the world, acquired immunodeficiency syndrome (AIDS) is an infectious disease distinct from other contagious diseases by its unique ways of transmission. Over the past few decades, research into new drug compounds has been accompanied by extensive advances, and the design and manufacture of drugs that inhibit virus enzymes is one way to combat the AIDS virus. Since blocking enzyme activity can kill a pathogen or correct a metabolic imbalance, the design and use of enzyme inhibitors is a new approach against viruses. We carried out an in-depth analysis of the efficacy of atazanavir and its newly designed analogs as human immunodeficiency virus (HIV) protease inhibitors using molecular docking. The best-designed analogs were then compared with atazanavir by the molecular dynamics simulation. The most promising results were ultimately found based on the docking analysis for HIV protease. Several exhibited an estimated free binding energy lower than -9.45 kcal/mol, indicating better prediction results than the atazanavir. ATV7 inhibitor with antiviral action may be more beneficial for infected patients with HIV. Molecular dynamics analysis and binding energy also showed that the ATV7 drug had more inhibitory ability than the atazanavir drug.

Preconcentration and determination of five antidepressants from human milk and urine samples by stir bar filled magnetic ionic liquids using liquid-liquid-liquid microextraction-high-performance liquid chromatography.

A sensitive and straightforward liquid-liquid-liquid microextraction method was developed to preconcentrate and cleanup antidepressants, including mirtazapine, venlafaxine, escitalopram, fluoxetine, and fluvoxamine, from biological samples before analyzing with high-performance liquid chromatography. The essential novelty of this study is using magnetic ionic liquids as the extraction phase in the lumen of hollow fiber and preparing a liquid magnetic stir bar. In this method, polypropylene hollow fiber was utilized as the permeable membrane for the analyte extraction. Six magnetic ionic liquids consisting of the transition metal and rare earth compounds were synthesized and then hollow fiber lumen was injected as acceptor phase to extract the antidepressants. Besides, 3-pentanol as a water-immiscible solvent was impregnated in the hollow fiber wall pores. The effective factors in the method were optimized with the central composition design. The resultant calibration curves were linear over the concentration range of 0.8-400.0 ng mL-1 (R2 ≥ 0.996). The method displayed the proper detection limit (0.11-0.24 ng mL-1 ), the reasonable limit of quantification (≤0.79 ng mL-1 ), wide linear ranges, high preconcentration factors (≥294.3), and suitable relative standard deviation (2.31-5.47%) for measuring antidepressant medications. Analysis of human milk and urine samples showed acceptable recoveries of 96.5-103.8% with excellent relative standard deviations lower than 5.95%.

Molecular Dynamics Simulations of Docetaxel Adsorption on Graphene Quantum Dots Surface Modified by PEG-b-PLA Copolymers.

Cancer is associated with a high level of morbidity and mortality, and has a significant economic burden on health care systems around the world in almost all countries due to poor living and nutritional conditions. In recent years, with the development of nanomaterials, research into the drug delivery system has become a new field of cancer treatment. With increasing interest, much research has been obtained on carbon-based nanomaterials (CBNs); however, their use has been limited, due to their impact on human health and the environment. The scientific community has turned its research efforts towards developing new methods of producing CBN. In this work, by utilizing theoretical methods, including molecular dynamics simulation, graphene quantum dots (GQD) oxide was selected as a carbon-based nanocarriers, and the efficiency and loading of the anticancer drug docetaxel (DTX) onto GQD oxide surfaces in the presence and in the absence of a PEG-b-PLA copolymer, as a surface modifier, were investigated. According to the results and analyzes performed (total energy, potential energy, and RMSD), it can be seen that the two systems have good stability. In addition, it was determined that the presence of the copolymer at the interface of GQD oxide delays the adsorption of the drug at first; but then, in time, both the DTX adsorption and solubility are increased.

Ultra-low concentration protein detection based on phenylalanine-Pd/SWCNT as a high sensitivity nanoreceptor.

Pd doped single-walled carbon nanotubes as an enhanced physical transducer with phenylalanine amino acid can be efficiently used as a biocompatible nanoreceptor to detect proteins. DFT/B3LYP was used to calculate the optimized geometries, energies and electron density parameters to determine the stability and reactivity of the nanoreceptor. Among different adsorbed configurations of phenylalanine, the amine and carboxylic acid sites have higher adsorption energies and more stable complexes. With direct strong chemical adsorption of phenylalanine amino acid onto the Pd doped single-walled carbon nanotube, the free active carboxylic acid group of the amino acid can react with free amine groups on the surface of the proteins. More over the π-π stacking interaction between the free aromatic ring of adsorbed phenylalanine amino acid onto the functionalized single-walled carbon nanotube and the aromatic rings of the proteins also contributes to the intelligent detection of proteins. Frontier molecular orbital and molecular electrostatic potential (MPE) surface studies have been employed to investigate the active sites of the nanoreceptor. The effects of different solvents on the structural and electronic properties were investigated. Finally, in order to investigate biological function of the biosensor, docking studies were performed.

Encapsulation efficiency of single-walled carbon nanotube for Ifosfamide anti-cancer drug.

The encapsulation efficiency of (10,10) armchair single-walled carbon nanotubes as a nanovector for Ifosfamide anti-cancer drug has been investigated. (10,10) armchair single-walled carbon nanotube was selected because of larger inner volume for encapsulation, distinct inner and outer surfaces for functionalization and penetration possibility into cells or cell nucleus. Moreover, the adverse side effects of Ifosfamide can be reduced by single-walled carbon nanotubes. A complete understanding of the encapsulation process of drug molecules into carbon nanotubes is necessary for drug delivery development. All possible stable conformers of the drug have been investigated through geometry optimizations at the B3LYP/6-31G**level of theory by using the Gaussian 09 suite of programs and then encapsulation of the most stable conformer has been studied. Results show that the Ifosfamide drug molecule can be encapsulated into the internal cavity of armchair single-walled carbon nanotube. The corresponding adsorption energy is -3.87 eV. Furthermore, the effects of encapsulation on the electronic properties of the carbon nanotube such as equilibrium distances, HOMO-LUMO energy gap and DFT based descriptors have been also probed. Quantum mechanical calculations of encapsulation verify that a single-walled carbon nanotube could adsorb an Ifosfamide molecule spontaneously via the chemisorption process.

Leucine/Pd-loaded (5,5) single-walled carbon nanotube matrix as a novel nanobiosensors for in silico detection of protein.

We have designed a novel nanobiosensor for in silico detecting proteins based on leucine/Pd-loaded single-walled carbon nanotube matrix. Density functional theory at the B3LYP/6-31G (d) level of theory was realized to analyze the geometrical and electronic structure of the proposed nanobiosensor. The solvent effects were investigated using the Tomasi's polarized continuum model. Atoms-in-molecules theory was used to study the nature of interactions by calculating the electron density ρ(r) and Laplacian at the bond critical points. Natural bond orbital analysis was performed to achieve a deep understanding of the nature of the interactions. The biosensor has potential application for high sensitive and rapid response to protein due to the chemical adsorption of L-leucine amino acid onto Pd-loaded single-walled carbon nanotube and reactive functional groups that can incorporate in hydrogen binding, hydrophobic interactions and van der Waals forces with the protein surface in detection process.

Nanocarrier for levodopa Parkinson therapeutic drug; comprehensive benserazide analysis.

Loss of dopamine-secreting neurons in the midbrain causes Parkinson's disease. L-DOPA, the precursor to the neurotransmitters dopamine, crosses vast majority of physiological and biochemical barriers that dopamine cannot. But most levodopa is decarboxylated to dopamine before it reaches the brain. This causes to little therapeutic gain with strong peripheral side effects. Benserazide is an irreversible inhibitor of peripheral aromatic L-amino acid decarboxylase that prevents the breakdown of levodopa in the bloodstream. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of Levodopa drug. Biocompatible nano-sized drug carriers could address these challenges at molecular level. Thus calculations of drug loading ability of acid-functionalized CNT for the benserazide as a nanodug carrier complex for L-DOPA were performed. In this regard, evaluation of all adsorption features of the most stable conformer of benserazide molecule onto carboxylated carbon nanotube is critical. To determine the minimum energy conformer of benserazide, the molecular structure and conformational analysis of 512 possible conformers have been subjected to first principle quantum mechanical calculations. Our work established a novel and easy-to-make formulation of benserazide/carboxylated CNT conjugate with extremely high drug loading efficiency of Levodopa for Parkinson disease treatment.