Popular Nonsteroidal Anti-inflammatory Drug Research Articles

Current challenges for therapy of comorbid patients: a new look at celecoxib. A review

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.

Photocatalytic degradation of naproxen using TiO2 single nanotubes

Herein, TiO2 single-tube (TiO2 ST-NT) powders with and without magnetite Fe3O4 nanoparticles (TiO2 ST-NT@Fe3O4NPs) are presented for the first time as excellent photocatalysts for the degradation of one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs), naproxen (NPX). The TiO2 ST-NT powders were synthesized by anodization followed by etching of the double wall, bending, sonication, ultra-centrifugation, and finally annealing at 600°C. A part of the obtained TiO2 ST-NT powders was decorated with Fe3O4 nanoparticles using a simple one-step decoration process. The best photocatalytic performance of TiO2 ST-NT and TiO2 ST-NT@Fe3O4NPs powders was obtained under the white light (6.2 × 10−4 s-1) and the blue light (2.7 × 10−4 s-1), respectively. During NPX photodegradation using TiO2 ST-NT powders, three main NPX transformation products (P1, P2, and P3) were detected. Upon excitation with the blue light illumination, TiO2 ST-NT@ Fe3O4NPs powders exhibited higher performance (∼80%) than TiO2 ST-NT powders (∼23%) within 1 h, resulting in an approximately three times increased photocatalytic rate constant. Moreover, under simulated sunlight conditions, TiO2 ST-NT powders demonstrated remarkable activity, achieving a 94% NPX degradation within 1 h. TiO2 ST-NT and TiO2 ST-NT@Fe3O4NPs powders represent excellent photocatalysts for NPX degradation.

Naproxen as environmental pollution, its effect on bacteria metabolism and degradation mechanism in immobilized Planococcus sp. S5

Planococcus sp. S5 belongs to strains that degrade naproxen, one of the most popular non-steroidal anti-inflammatory drugs. In the presented work, the immobilization of the S5 strain was carried out on the Loofah plant sponge, which improved the degradation efficiency, and kinetic studies indicated the abolition of the inhibition by the substrate observed in the free cell system. At the same time, after immobilization, evident changes were observed in the metabolic profile of the strain, which was related to the specific microenvironment of the carrier. The study also presents the naproxen degradation pathway in a system with the immobilized S5 strain for the first time. The analysis of intermediates formed during the decomposition of naproxen indicated that this decomposition occurs through naphthalene and salicylic acid. Furthermore, the degradation of naproxen via 3-hydroxybenzoic acid to gentisic acid is also possible. The high efficiency of naproxen degradation by the immobilised S5 strain enables its use in bioremediation.

Low cross-linked terpenes-based porous polymers with reduced content of divinylbenzene: synthesis, physicochemical properties and sorption abilities

The low cross-linked porous polymers were prepared using terpene compounds (citral, limonene and pinene) and divinylbenzene with a suspension method. The prepared materials were characterized by: ATR-FTIR, low temperature nitrogen adsorption–desorption, TGA, swelling ratio and solid phase extraction (SPE) experiments. ATR-FTIR verified the chemical structures of the polymers. All the materials had developed internal structure with SBET in the range of 45–190 m2/g and high thermal stability. Sorption properties of the terpene-based polymers were tested for phenolic compounds (phenol, 2-chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol) and popular non-steroidal anti-inflammatory drugs (aspirin, paracetamol and ibuprofen) and an antibiotic (ampicillin) with a dynamic solid phase extraction (SPE) method. The recoveries of 2,4-dichlorophenol and 2,4,6-trichlorophenol remained at a level 80–100% for all new materials even for 10–13 concentration cycles. Very high recoveries (70–100%) were also obtained for ibuprofen and aspirin from the citral- and limonene-based polymers using one-component solutions. However, when using ternary component solutions, the maximum recoveries of ibuprofen reached 70%. Paracetamol recoveries did not exceed 20%, while these for ampicillin ranged from 40 to 80%. The performed studies have proven that the process is affected by both chemical nature of adsorbents and adsorbates. Especially in the case of multicomponent solutions, the acid—base balance of solutes in the solution and on the polymer—solution interface should be taken into account as an important factor determining obtained recoveries.

Acetylsalicylic Acid Supplementation Affects the Neurochemical Phenotyping of Porcine Duodenal Neurons.

Aspirin (ASA) is a popular nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic properties through the inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA results in the formation of gastrointestinal side effects. Due to the fact that the enteric nervous system (ENS) is involved in the regulation of digestive functions both in physiological and pathological states, the aim of this study was to determine the influence of ASA on the neurochemical profile of enteric neurons in the porcine duodenum. Our research, conducted using the double immunofluorescence technique, proved an increase in the expression of selected enteric neurotransmitters in the duodenum as a result of ASA treatment. The mechanisms of the visualized changes are not entirely clear but are probably related to the enteric adaptation to inflammatory conditions resulting from aspirin supplementation. A detailed understanding of the role of the ENS in the development of drug-induced inflammation will contribute to the establishment of new strategies for the treatment of NSAID-induced lesions.

Diclofenac Biodegradation by Microorganisms and with Immobilised Systems—A Review

Diclofenac is one of the most popular non-steroidal anti-inflammatory drugs. Due to its over-the-counter availability and high consumption along with municipal and hospital wastewater, it enters the sewage treatment plant, where it is not completely degraded. This results in the appearance of diclofenac in the effluents from the treatment plant, and with them, it enters the surface waters. Due to its structure, it is characterised by its high resistance to degradation in the environment. At the same time, it shows documented acute and chronic toxicity to non-target organisms. For this reason, it is necessary to look for cheap solutions that enhance the degradation of diclofenac. The paper discusses both the pathways of microbiological degradation of this drug described so far, as well as modern systems of biocatalyst immobilisation, with a particular emphasis on laccases involved in the biotransformation of diclofenac.

Structural Investigation of Diclofenac Binding to Ovine, Caprine, and Leporine Serum Albumins.

Free drug concentration in the blood sera is crucial for its appropriate activity. Serum albumin, the universal blood carrier protein, is responsible for transporting drugs and releasing them into the bloodstream. Therefore, a drug's binding to SA is especially important for its bioavailability and it is a key problem in the drug design process. In this paper, we present crystal structures of three animal serum albumin complexes: ovine, caprine, and leporine, with diclofenac, a popular non-steroidal anti-inflammatory drug that is used in therapy of chronic and acute pain. Details of diclofenac binding mode by the presented serum albumins are compared with analogous complexes of human and equine serum albumins. The analysis of the occupied binding pockets in crystal structures of the investigated serum albumins from different mammals shows that they have two common and a number of unique diclofenac binding sites. The most intriguing is the fact that the albumins from the described species are able to bind different numbers of molecules of this popular anti-inflammatory drug, but none of the binding sites overlap with ones in the human serum albumin.

Removal of diclofenac by adsorption process studied in free-base porphyrin Zr-metal organic frameworks (Zr-MOFs).

As the world population continues to grow, there is also a rising concern regarding water pollution since this condition could negatively impact the supply of clean water. One of the most recent concerns is related to the pollution that comes from various pharmaceuticals, in particular non-steroidal anti-inflammatory drugs (NSAIDs) since they have been industrially produced at large scale and can be easily purchased as an over-the-counter medicine. Diclofenac is one of the most popular NSAIDs because of its high-effectiveness, which leads to its excessive consumption. Consequently, its presence in water bodies is also continuously increasing. An adsorption process could then be employed as a highly effective method to address this issue. In comparison to other conventional adsorbents such as activated carbon, the use of metal-organic frameworks (MOFs) as an alternative adsorbent is very attractive since it can offer various advantages such as tailorability and high adsorption capacity. In this study, the performance of three water-stable, free-base porphyrin MOFs assembled using zirconia-based nodes, namely MOF-525, MOF-545, and NU-902, for diclofenac adsorption was thoroughly investigated. Interestingly, although all three free-base porphyrin MOFs are assembled using the same building block and have a similar specific surface area (based on the experimental argon physisorption and calculation based on non-localized density functional theory), their diclofenac adsorption capacity is substantially different from one another. It is found that the highest diclofenac adsorption capacity is shown by MOF-525, which has maximum capacity around 792 mg g-1. This is then followed by MOF-545 and NU-902 that have adsorption capacities around 591 and 486 mg g-1, respectively. Some possible adsorption mechanisms are then thoroughly discussed that might contribute to this phenomenon. Lastly, their performance is also compared with other MOFs that are also studied for this purpose to show their performance superiority not only in terms of adsorption capacity but also their affinity towards the diclofenac molecule, which might be useful as an adsorption performance indicator in the real condition where the contaminant concentration is considerably low.

Synthesis of defective MOF-801 via an environmentally benign approach for diclofenac removal from water streams

Diclofenac is one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs) which has been widely used worldwide. Despite its popularity, its accumulation in the environment poses danger to the aquatic lives and its removal from the environment is paramount important. Although some conventional adsorbents such as activated carbon can be readily used to address this issue, they usually suffer from low diclofenac adsorption capacity (around 200 mg g−1), resulting in bulky adsorption systems. To overcome this problem, high performance materials such as metal organic frameworks (MOFs) can be employed. Here, we report that we synthesised defective MOF-801 for enhanced diclofenac adsorption via a simple and environmentally benign approach. Differing from a conventional MOF synthesis that usually requires the use of organic solvents at high temperature, the defective MOF-801 could be synthesised at room temperature and by changing the reaction medium from dimethylformamide to water. In addition, we have also successfully shown in this study that the defect concentration in MOF-801 can be rationally tuned by adjusting the modulator concentration (formic acid) in the synthesis solution. The resulting defective MOF-801 can then be used for environmental remediation, which we have shown here by employing them as an adsorbent for diclofenac removal from water streams. The enhanced adsorption of defective MOF-801 in comparison to its non-defective counterpart is due to the pore enlargement of the defective MOF-801 which provides a better pathway to access the adsorption sites. The maximum diclofenac adsorption capacity in a highly defective MOF-801 can reach as high as 680 mg g−1, which is almost 4 times higher than its non-defective counterpart. This study then opens possibilities to engineer the MOF particles for environmental remediation.

Organism-specific differences in the binding of ketoprofen to serum albumin.

Serum albumin is a circulatory transport protein that has a highly conserved sequence and structure across mammalian organisms. Its ligand-binding properties are of importance as albumin regulates the pharmacokinetics of many drugs. Due to the high degree of structural conservation between mammalian albumins, nonhuman albumins such as bovine serum albumin or animal models are often used to understand human albumin-drug interactions. Ketoprofen is a popular nonsteroidal anti-inflammatory drug that is transported by albumin. Here, it is revealed that ketoprofen exhibits different binding-site preferences when interacting with human serum albumin compared with other mammalian albumins, despite the conservation of binding sites across species. The reasons for the observed differences were explored, including identifying ketoprofen binding determinants at specific sites and the influence of fatty acids and other ligands on drug binding. The presented results reveal that the drug-binding properties of albumins cannot easily be predicted based only on a complex of albumin from another organism and the conservation of drug sites between species. This work shows that understanding organism-dependent differences is essential for assessing the suitability of particular albumins for structural or biochemical studies.

Photochemical Reaction of Ketoprofen with Proteinogenic Amino Acids.

Ketoprofen (KP) is one of the most popular nonsteroidal anti-inflammatory drugs; however, drug-induced photosensitivity of KP has been reported as a serious adverse effect. KP incorporated into a protein can produce an allergen under UV irradiation, which causes drug-induced photosensitivity. The photochemistry of KP with 20 kinds of proteinogenic amino acids in phosphate buffer solutions at pH 7.4 was studied by transient absorption spectroscopy. The KP carboxylate anion (KP-) gave rise to a carbanion via a decarboxylation within a laser pulse, and the carbanion yielded 3-ethylbenzophenone ketyl biradical (3-EBPH) through a proton transfer reaction. Twelve kinds of proteinogenic amino acids obviously accelerated the reaction. Structural information on the complexes of KP docked in the binding sites of human serum albumin (HSA) was obtained by molecular mechanics (MM) and molecular dynamics (MD) calculations. The photochemical reaction of KP- with amino acid residues in HSA was discussed on the basis of the experimental and calculational results. The information on the reactivity of KP with the amino acids and the stable structures of the KP-HSA complexes should be essential for understanding of the initial step for drug-induced photosensitivity.

Fourier Transform Infrared Spectroscopy and Vibrational Circular Dichroism Assisted Elucidation of the Solution-State Supramolecular Speciation in Racemic and Enantiopure Ketoprofen.

The molecular structure and solution-state molecular interactions in the popular non-steroidal anti-inflammatory drug, ketoprofen, are extensively studied with the aim of gaining a better understanding of the chemical behavior of its solution state and its connection to its nucleation pathway and crystallization outcome. Using as reference solid-state X-ray structures of enantiomeric and racemic forms of ketoprofen, a set of self-assembly models underpinned by density functional theory calculations has been considered for the analysis of spectroscopic data, infrared (IR) and vibrational circular dichroism (VCD), obtained for solutions of the samples as a function of composition and solvent. From our results it can be concluded that, contrary to the general belief for generic carboxylic acids, there are no cyclic dimeric structures of ketoprofen present in solution, but rather linear arrays made up of two (in high polar or diluted media) or more units (in low polar or low dilution media). This observation is in line with the idea that the weak contacts (other than H-bonding) would hold the key to molecular self-assembly, in agreement with recent studies on other aromatic carboxylic acids.

Development of effective potassium acetate extractant.

Carboxylates are commonly used in the food and pharmaceutical industry and due to their extensive use, carboxylates present a significant environmental burden. In this context, valine based, heteroditopic receptor 1 was prepared and its ability to bind simultaneously potassium cation and acetate anion in water containing CH3CN solutions was demonstrated. Under liquid–liquid extraction conditions the receptor 1 was capable of extracting hydrophilic AcOK salt from aqueous solution and was proved to be nearly ten times more effective than the equimolar mixture of monotopic receptors. Furthermore, compound 1 could extract one of the most popular nonsteroidal anti-inflammatory drugs, ibuprofen (IbuOK), from relatively dilute aqueous solutions.

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Clinical Implications

Effect of unimodality and bimodality of Pd nanoparticles on the catalytic activity of Pd/SiO2 in the removal of diclofenac from water

In this work, we investigated the catalytic performance of uni- and bimodal Pd/SiO2 catalysts in the aqueous phase hydrodechlorination (HDC) of diclofenac – a very popular nonsteroidal anti-inflammatory drug. Unimodality and bimodality was confirmed by temperature-programmed hydride decomposition (TPHD) and TEM. The highest activity and 100% efficiency in batch and flow mode were observed for bimodal Pd NPs. This outstanding efficiency could be attributed to the close coexistence of small and large metal nanoparticles with different affinity to hydrogen and chloroorganic compound. The obtained results encourage discussion on the necessity to strive for perfect unimodal catalysts for the HDC processes.

Degradation of diclofenac sodium using UV/biogenic selenium nanoparticles/H2O2: Optimization of process parameters

The resistance of diclofenac (DCF), one of the most popular nonsteroidal anti-inflammatory drugs, to biodegradation processes and its abundance in the aquatic environment made it an environmental concern. Degradation by ultraviolet (UV) irradiation in the presence of various catalysts has possibility to eliminate DCF from water resources. In the present study, optimization of DCF degradation under UV light irradiation using biogenic selenium nanoparticles (Se NPs) in the presence of H2O2 (assisted by central composite design) in a photoreactor followed by identification of the produced metabolites (using GC-MS (EI) technique) was evaluated. To assess the influence of parameters on the UV/Se NPs/H2O2-assisted degradation efficiency of DCF, four main factors including light intensity (W/m2), Se NPs concentration (μg/mL), pH, and H2O2 concentration (mM) were chosen. Predicted values of degradation efficiency were found to be in good agreement with experimental values (Pre-R2 = 0.9982 and Adj-R2 = 0.9953). Optimization results showed that maximum degradation efficiency (97.43%) was achieved at the optimum conditions including Se NPs concentration of 32 μg/mL, UV light intensity of 30 W/m2, pH 7.5, and H2O2 concentration of 0.05 mM. 1-(2, 6-dichlorophenyl)-2-indolinone was found to be the main product among several peaks in the GC-MS chromatogram of the DCF treated sample.

Selectivity Engineering in One-Pot Selective Synthesis of Drug Nabumetone over Novel Ni-Promoted La-Mg Oxide/Mesoporous Cellular Foam as Catalyst and Kinetic Modeling

One-pot synthesis of one of the popular non-steroidal anti-inflammatory drugs nabumetone (NBM) was achieved by using a novel catalyst. A series of mesoporous cellular foam (MCF) supported lanthanum...

Laboratory investigations of diclofenac migration in saturated porous media – a case study

Abstract At present, concentrations of pharmaceuticals in surface and ground waters are low; however, even low concentrations of certain substances may prove very harmful. One of such pharmaceutical drugs is diclofenac, a popular non-steroidal anti-inflammatory drug (NSAID). For this reason, it is important to determine its mobility in groundwater and to estimate parameters of migration. Authors conducted column tests for two porous media: an artificial one, consisting of glass granules, and a natural one, i.e., sandur sand obtained from a site north of the city of Poznań (Poland). During the test, impulse breakthrough curves of chloride ions and diclofenac were recorded. The results were used to identify a specific sorption model and to determine values of migration parameters. Solutions of the inverse problem using optimisation methods and of equations of mathematical migration models were carried out in a MATLAB environment. Based on test results, the mobility of diclofenac is shown to be very high and comparable to that of chloride ions. The tests also revealed a slight and irreversible sorption of diclofenac on grains of both porous media.

Hydrogen Abstraction of Ketoprofen in the Excited Triplet State with Indole and Methylindoles.

Relaxation of excited states and reactivity of ketoprofen (KP), one of the most popular nonsteroidal anti-inflammatory drugs, with indole and methylindoles have been studied with transient absorption and quantum chemical calculations. KP in the excited triplet state, 3KP*, abstracted a hydrogen atom from indole and methylindoles to afford a ketyl radical and a counter radical. The bimolecular quenching rate constants of 3KP* by indole and methylindoles, kq, and the hydrogen atom abstraction rate constants, kr, were obtained. The kr values for methylindoles were larger than that for indole; in addition, transient spectra at around 350 nm, assigned to the corresponding C-centered radical, was observed. These results indicate that 3KP* abstracts a hydrogen atom of the methyl group as well as that of N-H in the indole frame. These findings give us information on the reactivity of excited KP in the vicinity of tryptophan in a KP-protein complex, which will ultimately cause photosensitization on human skin.

Efficacy of removal of a popular NSAID from aqueous solutions with metalloligs

Acetaminophen, a popular NSAID (Non-steroidal anti-inflammatory drug), was studied for efficacy of removal from aqueous solutions. While Octolig® (a polyethylenediimine covalently attached to silica gel) is able to remove many simple anions and some acidic pharmaceuticals having a pKa value less than 4.5, it lacked efficacy with acetaminophen. Accordingly different transition- metal derivatives of Octolig® were tested by column chromatography using as substrates Octolig® derivatives of copper(II), cobalt(II), iron(III), manganese(II), nickel(II), and zinc(II).