Diclofenac-loaded PLGA nanoparticles downregulate LasI/R quorum sensing genes in pathogenic P. aeruginosa isolates.

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that can gradually and consistently release drugs in a controlled manner. In this study, diclofenac sodium-loaded PLGA nanoparticles (DS-PLGA NPs) were produced by solvent evaporation technique and characterized using SEM, DLS, and zeta potential analyses. The antibacterial and antivirulence potential of DS-PLGA NPs against P. aeruginosa strains were examined using broth microdilution, crystal violet staining, hemolysis, and twitching quantification assays. Furthermore, the expression of the quorum sensing (QS) genes, lasI and lasR in P. aeruginosa strains after treatment with 1/2 MIC of DS-PLGA NPs was assessed using real-time PCR. SEM imaging of the synthesized NPs exhibited that the NPs have a spherical structure with a size range of 60-150 nm. The zeta potential of the NPs was - 15.2 mV, while the size of the particles in the aquatic environment was in a range of 111.5-153.8 nm. The MIC of prepared NPs against various strains of P. aeruginosa ranged from 4.5 to 9 mg/mL. Moreover, exposure of bacteria to sub-MIC of DS-PLGA NPs significantly down-regulated the expression of the lasI and lasR genes to 0.51- and 0.75-fold, respectively. Further, prepared NPs efficiently reduced the biofilm formation of P. aeruginosa strains by 9-27%, compared with the controls. Besides, DS-PLGA NPs showed considerable attenuation in bacterial hemolytic activity by 32-88% and twitching motility by 0-32.3%, compared with untreated cells. Overall, the present work exhibited the anti-QS activity of DS-PLGA NPs, which could be a safe and useful approach for treating P. aeruginosa infections.

Diclofenac sodium effectively inhibits the biofilm formation of Staphylococcus epidermidis.

Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.

Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen.

BACKGROUND: Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques. METHODS: We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach. RESULTS: For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093. CONCLUSIONS: While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.

Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats.

These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.

Diclofenac sodium and paracetamol removal with ZnCl2 activated carbon produced from rice straw.

This study explored the efficacy of activated carbon derived from rice straw and treated with ZnCl2 (ZnCl2-RS) for the removal of diclofenac sodium (DCF) and paracetamol (PCM) through an adsorption process. The investigation included examining the variations in removal efficiency at different pH levels and ZnCl2-RS doses. The characteristics of the ZnCl2-RS, prepared for the study, were determined through SEM and FTIR analyses, revealing a composition of 49.4% carbon and 8.3% zinc. At pH 5, the adsorption efficiency for DCF and PCM was enhanced, achieving removal rates of 92.2% for DCF and 89.1% for PCM with 0.2 g of ZnCl2-RS. The adsorption of DCF and PCM by ZnCl2-RS followed pseudo-second-order kinetic and adhered to the Langmuir isotherm model. The maximum adsorption capacities were calculated as 26.04 mg/g for DCF and 19.05 mg/g for PCM. In conclusion, the cost-effective production of activated carbon from agricultural waste like rice straw yielded a promising adsorbent material for efficiently removing pharmaceuticals such as diclofenac sodium and paracetamol. This approach not only contributes to waste reduction but also promotes the repurposing of agricultural waste materials.

This study is about the preparation of rice straw, which is produced as agricultural waste, by ZnCl₂ activation and the usability of the prepared adsorbent material in the purification of drugs used as analgesics such as diclofenac sodium and paracetamol. Although there are studies on the use of activated carbon produced from rice straw in the removal of pollutants such as dye, studies on drug removal are quite limited.

Zingiber officinale Root Capsule Extract Synergistically Enhance the Anti-Inflammatory Effects of Diclofenac Sodium in Experimental Acute Inflammation.

The present study aimed to evaluate the anti-inflammatory effects of ginger (Zingiber officinale) root capsule extract (GRCE) in doses of 100 mg/kg b.w. (body weight) and 200 mg/kg b.w. alone and in combination with a low dose (5 mg/kg b.w.) of diclofenac sodium (D) on carrageenan-induced acute inflammation (AI). The association of GRCE in a dose of 200 mg/kg b.w. with D offered the highest inhibition percentage for edema, reaching the maximum level of inhibition (95%) after 24 h. The association of GRCE in a dose of 200 mg/kg b.w. with D showed the ability to reduce tissue inflammatory changes when compared to D alone, while GRCE alone did not exhibit such properties. The association of both doses of GRCE with D showed significantly lower plasma and tissue levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by up to 55% (p ≤ 0.0317), with the best results obtained by the group who received GRCE in the higher dose. These associations reduced the serum and tissue levels of prostaglandin-endoperoxide synthase 2 (COX-2) by up to 71% (p ≤ 0.0371). In conclusion, the association of GRCE with a low dose of D could be an appropriate combination to decrease the dose used to reduce serum and tissue levels of inflammatory molecules, edema, and histological changes in acute inflammation. Further research will be necessary to achieve clinical evaluation.

Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction.

Based on the synergistic action of hydrogen bond and electrostatic interaction, provided by methacrylic acid and 2-aminoethyl ester hydrochloride (FM2), respectively, novel molecularly imprinted polymers (SA-MIPs) were designed to improve its selective recognition ability. Diclofenac sodium (DFC) was chosen as the template molecule of this study. The interaction and their recognition sites between two functional monomers and templates were confirmed by nuclear magnetic resonance hydrogen spectroscopy. Because of the synergistic action of hydrogen bond and electrostatic interaction, the imprinting factor (IF) of SA-MIPs (IF = 2.26) is superior to the corresponding monofunctional monomer imprinting materials (IF = 1.52, 1.20) and the materials using two functional monomers with an only single type of interaction (IF = 1.54, 1.75). The results of selective adsorption experiments indicate that the selective recognition ability of SA-MIPs is significantly better than that of the other four MIPs, and the difference in selectivity coefficient for methyl orange is the largest between SA-MIPs and the MIPs only using FM2, which is about 70 times. In addition, x-ray photoelectron spectroscopy was used to verify the interaction between SA-MIPs and the template. This work and its explanation of the interaction mechanism at the molecular level will be helpful for the rational design of novel MIPs with higher selectivity. Besides, SA-MIPs have good adsorption performance (37.75 mg/g) for DFC in aqueous solutions, which could be used as potential adsorption materials for the effective removal of DFC in the aquatic environment.

Effects of Diclofenac Sodium on Seizure Activity in Rats with Pentylenetetrazole-Induced Convulsions.

Epilepsy is a disease which affects between 1 and 2% of the population, and a large proportion of these people do not react to currently available anticonvulsant medications, indicating the need for further research into novel pharmacological therapies. Numerous studies have demonstrated that oxidative stress and inflammation occur during epilepsy and may contribute to its development and progression, indicating higher levels of oxidative and inflammatory parameters in experimental models and clinical patients. This research aimed to assess the impact of diclofenac sodium, a nonsteroidal anti-inflammatory medicine, on seizure and levels of oxidative stress and inflammatory biomarkers in a rat model of epilepsy triggered by pentylenetetrazole (PTZ). 60 rats were randomly allocated to one of two groups: electroencephalography (EEG) recordings or behavioral evaluation. Rats received diclofenac sodium at three various doses (25, 50, and 75 mg/kg) intraperitoneally (IP) or a placebo, followed by intraperitoneal (IP) pentylenetetrazole, a powerful seizure-inducing medication. To investigate if diclofenac sodium had antiseizure properties, seizure activity in rats was evaluated using EEG recordings, the Racine convulsion scale (RCS) behaviour score, the duration of the first myoclonic jerk (FMJ), and the levels of MDA, TNF-α, and SOD. The average percentage of EEG spike waves decreased from 76.8% (placebo) to 64.1% (25 mg/kg diclofenac), 55.9% (50 mg/kg diclofenac), and 37.8% (75 mg/kg diclofenac). FMJ had increased from a mean of 58.8 s (placebo), to 93.6 s (25 mg/kg diclofenac), 185.8 s (50 mg/kg diclofenac) and 231.7 s (75 mg/kg diclofenac). RCS scores decreased from a mean score of 5.6 (placebo), to 3.75 (25 mg/kg diclofenac), 2.8 (50 mg/kg diclofenac) and 1.75 (75 mg/kg diclofenac). MDA levels reduced from 14.2 ng/gr (placebo) to 9.6 ng/gr (25 mg/kg diclofenac), 8.4 ng/gr (50 mg/kg diclofenac) and 5.1 ng/gr (75 mg/kg diclofenac). Likely, TNF-α levels decreased from 67.9 ng/gr (placebo) to 48.1 ng/gr (25 mg/kg diclofenac), 33.5 ng/gr (50 mg/kg diclofenac) and 21.3 ng/gr (75 mg/kg diclofenac). SOD levels, however, enhanced from 0.048 U/mg (placebo) to 0.055 U/mg (25 mg/kg diclofenac), 0.14 U/mg (50 mg/kg diclofenac), and 0.18 U/mg (75 mg/kg diclofenac). Diclofenac sodium (25, 50, and 75 mg/kg i.p.) effectively lowered the spike percentages and RCS scores linked with PTZ-induced epilepsy in rats, as well as significantly decreased MDA, TNF-α, IL-1ß, PGE2 and increased SOD levels. Probably as a result of its anti-oxidative and anti-inflammatory effects, diclofenac sodium dramatically lowered seizure activity at both doses compared to placebo control. Each of these results were significant, with p-values of < 0.01, < 0.05. Therefore, the therapeutic application diclofenac sodium as a potential anticonvulsant should be investigated further.

Self-cleaning cellulose acetate/crystalline nanocellulose/polyvinylidene fluoride/Mg0.975Ni0.025SiO3membrane for removal of diclofenac sodium and methylene blue dye in water.

Recalcitrant pollutants present in wastewater, without an effective treatment, have several effects on aquatic ecosystems and human health due to their chemical structure and persistence. Therefore, it is crucial the development of efficient technologies to eliminate such pollutants in water. Nano-photocatalysts are considered a promising technology for water remediation; however, one common drawback is the difficulty of recovering it after water processing. One effective strategy to overcome such problem is its immobilization into substrates such as polymeric membranes. In this study, a polymeric membrane with embedded Mg0.975Ni0.025SiO3is proposed to remove model pollutants diclofenac sodium and methylene blue dye by synergetic adsorption and photocatalytic processes. Mg0.975Ni0.025SiO3was synthesized by the combustion method. The matrix polymeric blend consisting of a blend of cellulose acetate, crystalline nanocellulose and polyvinylidene fluoride was obtained by the phase inversion method. The composite membranes were characterized by FTIR, x-ray diffraction, and scanning electron microscopy. With pollutant solutions at pH 7, the pollutant adsorption capacity of the membranes reached up to 30% and 45% removal efficiencies for diclofenac sodium and methylene blue, respectively. Under simulated solar irradiation photocatalytic removal performances of 70% for diclofenac sodium pH 7, and of 97% for methylene blue dye at pH 13, were reached. The membrane photocatalytic activity allows the membrane to avoid pollutant accumulation on its surface, given a self-cleaning property that allows the reuse of at least three cycles under sunlight simulator irradiation. These results suggest the high potential of photocatalytic membranes using suitable and economical materials such as cellulosic compounds and magnesium silicates for water remediation.

NFK prevent postoperative abdominal adhesion through downregulating the TGF-ß1 signaling pathway.

BACKGROUND: Postoperative abdominal adhesions (PAAs) represent a frequent condition occurring in more than 90% of patients undergoing abdomen and pelvic surgeries, which can cause chronic abdominal pain, female infertility, and repeated bowel obstruction, requiring repetitive surgical interventions causing morbidity and mortality, as well as high costs. It is therefore of paramount clinical importance and significance to develop practical and reliable strategies for preventing the occurrence of PAAs. METHODS AND RESULTS: In this study, we demonstrated that Nianfukang (NFK, composed of polyethylene glycol 1450 and diclofenac sodium) is highly effective in preventing PAAs, likely by reducing leukocytes and inflammatory factors in the abdominal cavity, and inhibiting intestinal fibrosis in a rat model of PAAs induced by postoperative cecum scraping. We further uncovered that NFK downregulates the expression of TGF-ß1, a key factor for adhesion formation, to suppress the TGF-ß1/TGF-ßRIII/Smad2 signaling pathway, thereby inhibiting the proliferation and migration of fibroblasts and provided evidences for the involvement of the TGF-ß1/TGF-ßRIII/Smad2 axis in the prevention of PAAs in normal human colon fibroblast CCD-18Co. CONCLUSIONS: Our findings support NFK as a potential anti-adhesive product that has the advantages of significant effectiveness, safety profile, and low cost, as well as clear mechanism of action.

Development of zinc ferrite nanoparticles with enhanced photocatalytic performance for remediation of environmentally toxic pharmaceutical waste diclofenac sodium from wastewater.

Diclofenac sodium is an anti-inflammatory drug commonly used to cure pain in various treatments. The remarkable potential of this pain-killer leads to its excessive use and, therefore, a persistent water contaminant. Its presence in aqueous bodies is hazardous for both humans and the environment because it causes the growth of harmful drug-resistant bacteria in water. Herein, we present a comparative study of the ZnO and ZnFe2O4 as photocatalysts for the degradation of diclofenac sodium, along with their structural and morphological studies. A simple co-precipitation method was used for the synthesis of ZnO and ZnFe2O4 and characterized by various analytical techniques. For instance, the UV-Vis study revealed the absorption maxima of ZnO at 320 nm, which was shifted to a longer wavelength region at 365 nm for zinc ferrite. The optical band gaps obtained from the Tauc plot indicated that the incorporation of iron has led to a decreased band gap of zinc ferrite (2.89 eV) than pure ZnO (3.14 eV). The metal-oxygen linkages shown by FTIR indicated the formation of desired ZnO and ZnFe2O4, which was further confirmed by XRD. It elucidated the typical hexagonal structure for ZnO and spinel cubic structure for ZnFe2O4 with an average crystallite of 31 nm and 44 nm for ZnO and ZnFe2O4, respectively. The micrographs obtained by SEM showed rough spherical particles of ZnO, whereas for ZnFe2O4 flower-like clustered particles were observed. The photocatalytic investigation against diclofenac sodium revealed the higher degradation efficiency of ZnFe2O4 (61.4%) in only 120 min, whereas ZnO degraded only 48.9% of the drug. Moreover, zinc ferrite has shown good recyclability and was stable up to five runs of photodegradation with a small loss (3.9%) of photocatalytic activity. The comparison of two catalysts has suggested the promising role of zinc ferrite in wastewater remediation to eliminate hazardous pharmaceuticals.

CDCT-induced nephrotoxicity in rat by apoptosis via metabolic disturbance.

Compound diclofenac sodium chlorphenamine maleate tablets (CDCT) are widely used for the cold in Asia. However, CDCT can cause hematuria symptoms in clinical, and the underlying mechanism is unknown. This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites and further explore the possible mechanisms of CDCT-induced nephrotoxicity. Sprague-Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6 days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen, and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolites, such as succinate, leukotriene B4 (LTB4 ), and cardiolipin (CL), are observed in the CDCT-induced nephrotoxicity. Functionally, succinate accumulation leads to mitochondrial damage, as evidence by the imbalance of complex I and complex II and an increase in mitochondrial reactive oxygen species (mito SOX). Meanwhile, LTB4 activated the NF-κB signaling, as shown by increased protein of p65, phosphor-p65, and decreased protein of IκBα and phosphor-IκBα. Eventually, the apoptosis pathway was triggered in response to reduced CL, inflammation, and mito SOX, as demonstrated by the expression of cyt c, Bax, Bcl-2, caspase-3, and caspase-9. This study indicated that CDCT-induced metabolic disorders triggered nephrotoxicity and provided a comprehensive information to elucidate the mechanism of CDCT induced nephrotoxicity.

Exploring the Drug-Loading and Release Ability of FucoPol Hydrogel Membranes.

The polysaccharide FucoPol has recently been shown to yield hydrogel membranes (HMs) characterized by good mechanical properties, biocompatibility, and anti-inflammatory activity that render them promising biomaterials for use in the biomedical field. Subsequently to such findings, envisaging their development into novel delivery systems for topical applications, in this study, FucoPol HMs prepared by crosslinking the biopolymer with iron cations were loaded with caffeine or diclofenac sodium as model drugs. Two loading methods, namely diffusion and mixing, were applied to evaluate the FucoPol's HM drug-loading capacity and entrapment efficiency. The diffusion method led to a higher caffeine loading (101.9 ± 19.1 mg/g) in the HM1_DCAF membranes, while the mixing method resulted in a higher diclofenac sodium loading (82.3 ± 5.1 mg/g) in the HM1_DDS membranes. The HM1_DCAF membranes were characterized by increased mechanical and rheological parameters, such as their hardness (130.0 ± 5.3 kPa) and storage modulus (1014.9 ± 109.7 Pa), compared to the HM1_DDS membranes that exhibited lower values (7.3 ± 1.2 kPa and 19.8 ± 3.8 Pa, respectively), probably due to leaching occurring during the drug-loading process. The release profiles revealed a fast release of both APIs from the membranes loaded by diffusion, while a prolonged and sustained release was obtained from the membranes loaded by mixing. Moreover, for all API-loaded membranes, the release mechanism followed Fickian diffusion, with the release rate being essentially governed by the diffusion process. These findings, together with their previously shown biological properties, support the suitability of the developed FucoPol HMs to be used as platforms for the topical delivery of drugs.

Characteristics of Interpolyelectrolyte Complexes Based on Different Types of Pectin with Eudragit® EPO as Novel Carriers for Colon-Specific Drug Delivery.

Given that pectin is a well-known substance used for drug delivery, we aimed to obtain and further examine the efficacy of interpolyelectrolyte complexes based on citrus or apple pectin and the Eudragit® EPO for using these carriers in oral drug delivery. To characterize the physicochemical properties of these compounds, turbidity, gravimetry, viscosity, elementary analysis, FTIR spectroscopy, and DSC analysis were utilized. Diffusion transport characteristics were evaluated to assess the swelling ability of the matrices and the release of diclofenac sodium. To examine the release parameters, mathematical modeling was performed by using the Korsmayer-Peppas and Logistic equations as well. During the turbidity study, stoichiometry compositions were selected for the developed IPECs EPO/PecA and EPO/PecC at pH values = 4.0, 5.0, 6.0, and 7.0. The FTIR spectra of the complexes were characterized by an increase in the intensity of the bands at 1610 cm-1 and 1400 cm-1. According to the DSC analysis, IPEC has a certain Tg = 57.3 °C. The highest release rates were obtained for IPEC EPO/PecC_1 and EPO/PecC_4. The mechanism of drug transport from the matrices IPEC EPO/PecC, IPEC EPO/PecA_3, and EPO/PecA_4 can be characterized as Super Case II. Anomalous release (non-Fickian release) is typical for IPEC EPO/PecA_1 and EPO/PecA_2. Thus, the resulting systems can be further used for the effective delivery of the drugs to the colon.

A Carboxyl Group-Functionalized Ionic Liquid Hybrid Adsorbent for Solid-Phase Extraction and Determination of Trace Diclofenac Sodium in Milk Samples.

A simple and efficient sample pretreatment technology is very important for the accurate determination of trace drug residues in foods to ensure food safety. Herein, we report a new carboxyl group-functionalized ionic liquid hybrid solid- phase adsorbent (PS-IL-COOH) for the highly efficient extraction and quantitative determination of diclofenac sodium (DS) residue in milk samples. It was found that the adsorption efficiency of PS-IL-COOH for the ppb level of DS was greater than 93.0%, the adsorption capacity was 934.1 mg/g, and the enrichment factor was 620.0, which surpass most of the previously reported values for DS adsorbents. The high concentration of salts did not interfere with the adsorption of DS. Importantly, the recovery of DS was above 90% after 16 adsorption--regeneration cycles. The synergistic effect of the multiple interactions was found to be the main factor for the high efficiency of DS adsorption. The proposed method was applied to the extraction and detection of DS in milk samples, with the relative recovery ranging from 88.2 to 103.0%.

Environmental Risk Assessment of Drugs in Tropical Freshwaters Using Ceriodaphnia silvestrii as Test Organism.

In this study we evaluated the acute (immobility/mortality) and chronic (survival and reproduction) effects of the drugs caffeine, diclofenac sodium salt, ketoprofen, paracetamol and salicylic acid on the cladoceran Ceriodaphnia silvestrii. The environmental risks of these substances for tropical freshwaters were estimated from the risk quotient MEC/PNEC. Sensitivity in acute exposures varied up on the drug as follows: salicylic acid (EC50 = 69.15 mg L- 1) < caffeine (EC50 = 45.94 mg L- 1) < paracetamol (EC50 = 34.49 mg L- 1) < ketoprofen (EC50 = 24.84 mg L- 1) < diclofenac sodium salt (EC50 = 14.59 mg L- 1). Chronic toxicity data showed negative effects of the drugs on reproduction. Paracetamol and salicylic acid caused reduction in fecundity in concentrations starting from 10 mg L- 1 and 35 mg L- 1, respectively. Ketoprofen caused total inhibition at 5 mg L- 1. MEC/PNEC values were relatively low for all drugs. The risk was estimated as low or insignificant, except for caffeine, whose MEC/PNEC value was greater than 1 (moderate risk).

Study of the anti-inflammatory properties of a thick extract of Tribulus terrestris L.

The most promising direction in the treatment of chronic prostatitis is the use of medicinal plants and preparations based on them, which contain natural compounds with a broad spectrum of pharmacological activity: anti-inflammatory, antimicrobial, reparative, immunomodulatory, hormone-regulating, antisclerotic, etc., and which can provide a complex therapeutic effect on the course of chronic prostatitis. A promising raw material in this direction is Tribulus terrestris L., a herbal preparation traditionally used to treat erectile dysfunction and atherosclerosis. This experimental work aims to study the anti-inflammatory activity of a thick extract of the Tribulus terrestris grass (freed from fruits) on the models of carrageenan and zymosan inflammation in rats. In the models of carrageenan and zymosan edema in rats, a thick extract of Tribulus terrestris L. in doses from 50 mg/kg to 200 mg/kg shows anti-inflammatory activity, the efficacy of which in the dose range of 150-200 mg/g in the initial stages of carrageenan inflammation is not inferior to sodium diclofenac at a dose of 8.0 mg/kg, and in the initial stages of zymosan inflammation, respectively, before the reference drug corvitin at a dose of 10 mg/kg. It indicates the anticyclogenase and antilipoxygenase properties of this thick extract.

Six-Step Continuous Flow Synthesis of Diclofenac Sodium via Cascade Etherification/Smiles Rearrangement Strategy: Tackling the Issues of Batch Processing.

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) as over-the-counter (OTC) medication for the treatment of inflammatory diseases. Herein, the development of an intensified six-step continuous flow synthesis of diclofenac sodium from commercially available aniline and chloroacetic acid is described. A challenging and unprecedented etherification/Smiles rearrangement cascade of 2-chloro-N-phenylacetamide and 2,6-dichlorophenol into hydroxyacetyldiphenylamine operated with the precise control of reaction conditions in continuous flow was realized as the key step in this multistep synthetic chemistry. The undesired amide hydrolysis in Smiles rearrangement was addressed and the extra installation of N-chloroacetyl group in current industrial batch mode was avoided. Diclofenac sodium was obtained in 63 % isolated yield with an average yield of above 90 % for each step in a total residence time of 205 min.

Self-administered subcutaneous diclofenac sodium in acute migraine attack: A randomized, double-blind, placebo-controlled dose-finding pilot study.

BACKGROUND: A novel formulation of diclofenac, complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) as a solubility enhancer, in a prefilled syringe for self-administered subcutaneous injection may overcome the limitations of acute migraine treatments administered by oral, rectal, intramuscular, or intravenous routes. METHODS: This multicentre, phase 2, double-blind, randomized, placebo-controlled, dose-finding pilot study evaluated the efficacy, safety and tolerability of three different doses (25/50/75 mg/1 mL) of subcutaneous diclofenac sodium in the treatment of an acute migraine attack in 122 subjects. The primary efficacy endpoint was the percentage of patients pain-free at 2 hours after the study drug injection. RESULTS: A significantly higher percentage of patients in the 50 mg diclofenac group 14 (46.7%) were pain-free at 2 hours when compared with placebo: 9 (29.0%) (p = 0.01). The 50 mg dose proved superior to placebo also in the majority of the secondary endpoints. The overall global impression favoured diclofenac vs placebo. There were no adverse events leading to study withdrawal. The majority of treatment-emergent adverse events were mild. CONCLUSIONS: The 50 mg dose of this novel formulation of diclofenac represents a valuable self-administered option for the acute treatment of migraine attacks.Trial registration: EudraCT Registration No. 2017-004828-29.

Mandarin peel ethanolic extract attenuates diclofenac sodium induced hepatorenal toxicity in rats by mitigating oxidative stress and inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute approximately one-third of the global pharmaceutical market and are the first drugs of choice when treating fever and pain. Furthermore, among NSAIDs, the use of diclofenac sodium (DS) is preferred as it is a strong inhibitor of cyclooxygenase enzyme. However, despite its strong efficacy, DS is known for its potential to cause hepatorenal damage. Currently, to mitigate the adverse effects of certain drugs, medically effective agricultural products are often preferred as they are inexpensive, effective and safe. One such agricultural product-mandarin-is noteworthy for its high phenolic contents. The purpose of the present study was to assess the efficacy of mandarin peel ethanolic extract (MPEE) in protecting against hepatorenal damage induced by DS. Four groups (six/group) of adult male albino rats received oral administration of physiological saline (control group), DS (10 mg/kg body weight), MPEE (200 mg/kg body weight), and DS + MPEE for 7 days. Rats in the DS group showed increased serum levels of ALT, AST, ALP, BUN, CRE, and UA. Furthermore, the hepatic and renal tissue levels of MDA, TNF-α and IL-1ß increased, whereas those of GSH, SOD, GP-x and IL-10 decreased (p < 0.05). Investigation of MPEE in terms of its effects on biochemical, oxidative and inflammatory parameters, it exerted protective and healing effects. Therefore, MPEE can be used to ameliorate DS-induced hepatorenal damage.