Topical Diclofenac Reduces Joint Synovitis in Hand Osteoarthritis: A Pilot Investigation Using Fluorescent Optical Imaging.

Purpose: Synovitis, the inflammation of joint synovia, is a prominent feature of osteoarthritis (OA) manifested by enhanced synovial vascularity, endothelial leakage, and perivascular oedema. In this pilot study, we assessed the effect of topical diclofenac in hand OA (HOA) using the established semi-quantitative methods Magnetic Resonance Imaging (MRI) and Ultrasonography (US), and compared them with Fluorescent Optical Imaging (FOI), an emerging imaging modality. Patients and Methods: Ten patients with symptomatic and diagnosed HOA used topical diclofenac for 14 days, with FOI, MRI, US, and subjective pain assessed at Baseline and after 7 (Day 8), and 14 (Day 15) days of treatment. Changes in synovitis were assessed for all 10 joints of the hand (via sum scores), and separately for the two joints most affected by synovitis. A new, fully quantitative approach for objective synovitis assessment based on the FOI images was also developed and applied. Results: The semi-quantitative analysis of the sum scores showed a small decrease in synovitis throughout the treatment duration across the different imaging modalities. The effect of the treatment was more prominent on the two most affected joints, with a synovitis reduction vs Baseline of 21.1% and 34.2% on Day 8 and Day 15, respectively, in the FOI. The quantitative FOI pixel analysis further strengthened the evidence for this effect, with observed reduction of 17.8% and 42.4% for Days 8 and 15, respectively. A similar trend was observed for subjective pain perception, with a reduction of 7.2 and 13.3 mm on Days 8 and 15. Conclusion: This pilot study evidenced the effect of topical diclofenac on reducing synovitis in hand OA in semi- and fully quantitative analyses, with the effect being stronger in the most affected joints. Further, supporting studies are needed to probe the accuracy of the quantitative pixel analysis of FOI images.

Proteome profiling, biochemical and histological analysis of diclofenac-induced liver toxicity in Yersinia enterocolitica and Lactobacillus fermentum fed rat model: a comparative analysis.

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198 cm-1, while D*L rats lack peaks at 1411 cm-1. However, when compared to control, both groups lack peaks at 1379 and 1170 cm-1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC-MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity.

Melatonin protects against diclofenac induced oxidative stress mediated myocardial toxicity in rats: A mechanistic insight.

Diclofenac, a traditional non-steroidal anti-inflammatory drug, is commonly used for treating chronic pain and inflammation. Recently, a number of articles have highlighted the toxicities associated with diclofenac. The current study explores the molecular mechanism of diclofenac induced cardiac toxicity following oxidative stress. Diclofenac inhibits catalase, disrupts the redox balance in cardiac tissue, accelerates the monoamine oxidase induced hydroperoxide generation and eventually inhibits crucial mitochondrial enzyme, viz., aldehyde dehydrogenase, thereby causing myocardial injury. Melatonin, the pineal indoleamine with high antioxidative efficacy, is well known for its cardio-protective properties and its dietary consumption has profound impact on cardiac health. The present study demonstrates perhaps for the first time, that apart from ameliorating oxidative load in the cardiac tissue, melatonin also attenuates the inhibition of catalase and aldehyde dehydrogenase, and prevents stress mediated stimulation of monoamine oxidase. Moreover, favourable binding of diclofenac with melatonin may protect the myocardium from the deleterious effects of this drug. The results indicate toward a novel mechanism of protection by melatonin, having future therapeutic relevance.

Properties and Possibilities of Using Biochar Composites Made on the Basis of Biomass and Waste Residues Ferryferrohydrosol Sorbent.

Biochar enriched with metals has an increased potential for sorption of organic and inorganic pollutants. The aim of the research was to identify the possibility of using biochar composites produced on the basis of waste plant biomass and waste FFH (ferryferrohydrosol) containing iron atoms, after CO2 capture. The composites were produced in a one-stage or two-stage pyrolysis process. Their selected properties were determined as follows: pH, ash content, C, H, N, O, specific surface area, microstructure and the presence of surface functional groups. The produced biochar and composites had different properties resulting from the production method and the additive used. The results of experiments on the removal of methylene blue (MB) from solutions allowed us to rank the adsorbents used according to the maximum dye removal value achieved as follows: BC1 (94.99%), B (84.61%), BC2 (84.09%), BC3 (83.23%) and BC4 (83.23%). In terms of maximum amoxicillin removal efficiency, the ranking is as follows: BC1 (55.49%), BC3 (23.51%), BC2 (18.13%), B (13.50%) and BC4 (5.98%). The maximum efficiency of diclofenac removal was demonstrated by adsorbents BC1 (98.71), BC3 (87.08%), BC4 (74.20%), B (36.70%) and BC2 (30.40%). The most effective removal of metals Zn, Pb and Cd from the solution was demonstrated by BC1 and BC3 composites. The final concentration of the tested metals after sorption using these composites was less than 1% of the initial concentration. The highest increase in biomass on prepared substrates was recorded for the BC5 composite. It was higher by 90% and 54% (for doses of 30 g and 15 g, respectively) in relation to the biomass growth in the soil without additives. The BC1 composite can be used in pollutant sorption processes. However, BC5 has great potential as a soil additive in crop yield and plant growth.

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.

Hypothesizing the Oleic Acid-Mediated Enhanced and Sustained Transdermal Codelivery of Pregabalin and Diclofenac Adhesive Nanogel: A Proof of Concept.

Pregabalin and diclofenac diethylamine are anti-inflammatory molecules that are effective in relieving inflammation and pain associated with musculoskeletal disorders, arthritis, and post-traumatic pain, among others. Intravenous and oral delivery of these two molecules has their limitations. However, the transdermal route is believed to be an alternate viable option for the delivery of therapeutic molecules with desired physicochemical properties. To this end, it is vital to understand the physicochemical properties of these drugs, dosage, and strategies to enhance permeation, thereby surmounting the associated constraints and concurrently attaining a sustained release of these therapeutic molecules when administered in combination. The present work hypothesizes the enhanced permeation and sustained release of Pregabalin and diclofenac diethylamine across the skin, entrapped in the adhesive nano-organogel formulation, including permeation enhancers. The solubility studies of Pregabalin and diclofenac diethylamine in combination were performed in different permeation enhancers. Oleic acid was optimized as the best permeation enhancer based on in vitro studies. Pluronic organogel containing Pregabalin and diclofenac diethylamine with oleic acid was fabricated. Duro-Tak® (87-2196) was added to the organogel formulation as a pressure-sensitive adhesive to sustain the release profile of these two therapeutic molecules. The adhesive organogel was characterized for particle size, scanning electron microscopy, and contact angle measurement. The HPLC method developed for the quantification of the dual drug showed a retention time of 3.84 minutes and 9.69 minutes for pregabalin and diclofenac, respectively. The fabricated nanogel adhesive formulation showed the desired results with particle size and contact angle of 282 ± 57 nm and ≥120°, respectively. In vitro studies showed the percentage cumulative release of 24.90 ± 4.65% and 33.29 ± 4.81% for pregabalin and diclofenac, respectively. In order to accomplish transdermal permeation, the suggested hypothesis of fabricating PG and DEE nano-organogel in combination with permeation enhancers will be a viable drug delivery method. In comparison to a traditional gel formulation, oleic acid as a permeation enhancer increased the penetration of both PG and DEE from the organogel formulation. Notably, the studies showed that the use of pressure-sensitive adhesives enabled the sustained release of both PG and DEE.Therefore, the results anticipated the hypothesis that the transdermal delivery of adhesive PG and DEE-based nanogel across the human skin can be achieved to inhibit inflammation and pain.

Self-Assembled Multilayer-Modified Needles Simulate Acupuncture and Diclofenac Sodium Delivery for Rheumatoid Arthritis.

A novel therapeutic approach combining acupuncture and diclofenac sodium (DS) administration was established for the potential treatment for rheumatoid arthritis (RA). DS is a commonly used anti-inflammatory and analgesic drug but has short duration and adverse effects. Acupoints are critical linkages in the meridian system and are potential candidates for drug delivery. Herein, we fabricated a DS-loaded multilayer-modified acupuncture needle (DS-MMAN) and investigated its capacity for inhibiting RA. This DS-MMAN possesses sustained release properties and in vitro anti-inflammatory effects. Experimental results showed that the DS-MMAN with microdoses can enhance analgesia and efficiently relieve joint swelling compared to the oral or intra-articular administration of DS with gram-level doses. Moreover, the combination of acupoint and DS exerts a synergistic improvement in inflammation and joint damage. Cytokine and T cell analyses in the serum indicated that the application of DS-MMAN suppressed the levels of pro-inflammatory factors and increased the levels of anti-inflammatory factors. Furthermore, the acupoint administration via DS-MMAN could decrease the accumulation of DS in the liver and kidneys, which may express better therapeutic efficiency and low toxicity. The present study demonstrated that the acupuncture needle has the potential to build a bridge between acupuncture and medication, which would be a promising alternative to the combination of traditional and modern medicine.

Heterogeneous micellar solubilization within lyotropic liquid crystals interfaces.

The solubilization of sodium diclofenac (Na-DFC) in a glycerol monooleate-based emulsion triggers series of structural changes. Incorporation of Na-DFC, leads to formation of a reverse hexagonal mesophase between 2 and 5 wt% Na-DFC. Between 6 and 9 wt% Na-DFC, the hexagonal symmetry gradually transitions to a disordered lamellar mesophase. These structural shifts impact the system's storage modulus, structuring enthalpy, and structural diffusivity. Despite these transitions, the driving force for Na-DFC release remains consistent, leading to hypothesize that the interfacial structure remains unchanged during Na-DFC release. The nano-structural modifications imposed by the Na-DFC load and release were assessed by small-angle X-ray diffraction (SAXD), spin-probe electron paramagnetic resonance (EPR), and nuclear quadrupole resonance (NQR). The selective solubilization of Na-DFC was demonstrated by SAXD peak fittings, revealing an increase of hexagonally oriented rods at the expense of non-oriented micelles, rather than gradual micellar elongation. Computation of the EPR spectra also showcased the selective solubilization of Na-DFC at an enhanced free energy interface (γ), evidenced by step-wise variations in polarity, microviscosity, and order parameters. Additionally, NQR analysis highlighted a higher anisotropy for sodium compared to deuterium, linking the selective solubilization of Na-DFC to heterogeneous structural transformations. These findings underscore the heterogeneous nature of solubilization-release processes, driven by locally increased micellar free energy. Consequently, the loaded Na-DFC interfaces maintain a constant γ, ensuring a consistent release driving force despite the structural transitions affecting the matrix. The ability to selectively solubilize guest molecules may herald a new era in the utilization of selective molecular interfacial loading.

Functionalized fennel extract-mediated alumina/cerium oxide nanocomposite potentiometric sensor for the determination of diclofenac sodium medication.

The current work suggests a new, ultrasensitive green functionalized sensor for the determination of anti-inflammatory medication diclofenac sodium (DCF). Alumina (Al2O3) and cerium oxide (CeO2) nanoparticles (NPs) have attracted great interest for their use as outstanding and electroactive nanocomposite in potentiometric and sensory research due to their ultrafunctional potential. The formed nanoparticles have been confirmed using various spectroscopic and microscopic techniques. The fennel extract-mediated Al2O3/CeO2 nanocomposite (Al2O3/CeO2 NCS) modified coated wire membrane sensor developed in this study was used to quantify DCF in bulk and commercial products. Diclofenac sodium was coupled with phosphomolybdic acid (PMA) to generate diclofenac phosphomolybdate (DCF-PM) as an active ion-pair in the existence of polyvinyl chloride (PVC) and o-nitrophenyl octyl ether (o-NPOE). Clear peaks at 270, and 303 nm with band gaps of 4.59 eV and 4.09 eV were measured using UV-vis spectroscopy of Al2O3 and CeO2, respectively. The crystallite sizes of the formed nanoparticles were XRD-determined to be 30.13 ± 8, 17.72 ± 3, and 35.8 ± 0.5 nm for Al2O3, CeO2, and Al2O3/CeO2 NCS, respectively. The developed sensor showed excellent response for the measurement and assay of DCF, with a linearity between 1.0 × 10-9 and 1.0 × 10-2 mol L-1. EmV = (57.76) log [DCF] +622.69 was derived. On the other hand, the typical type DCF-PM presented a potentiometric response range of 1.0 × 10-5-1.0 × 10-2 mol L-1 and a regression equation of EmV = (56.97) log [DCF]+367.16. The functionalized sensor that was proposed was successful in determining DCF in its commercial tablets with percent recovery 99.95 ± 0.3. Method validation has been used to improve the suitability of the suggested potentiometric technique, by studying various parameters with respect to the international council harmonization requirements for analytical methodologies.

Antibacterial and antibiofilm activities of diclofenac against levofloxacin-resistant Stenotrophomonas maltophilia isolates; emphasizing repurposing of diclofenac.

Background and Objectives: Stenotrophomonas maltophilia is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates. Materials and Methods: Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; smeB, and smeF genes and biofilm related genes rmlA, spgM, and rpfF without and with diclofenac and the combination. Results: Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed smeB and smeF showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations. Conclusion: Diclofenac showed an antibacterial effect against Stenotrophomonas maltophilia. The combination showed in-vitro synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.

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.

A Structure-Based Design Strategy with Pyrazole-Pyridine Derivatives Targeting TNFα as Anti-inflammatory Agents: E-pharmacophore, Dynamic Simulation, Synthesis and In Vitro Evaluation.

Any pathogenic attack, infection, or disease can initiate inflammation. It results in significant adverse consequences like inflammatory bowel disease, rheumatoid arthritis, etc. TNFα is one of the major pro-inflammatory cytokines for the progression of inflammation-the present study designed a series of hybrid compounds consisting of the pyrazole-pyridine moiety. Virtual screening was performed utilizing the e-pharmacophore hypothesis with the co-ligand of TNFα, screening, docking, and ADMET study. Induced fit docking, DFT analysis, and molecular dynamic simulation showed that the four best molecules - Dh1- Dh4 - showed crucial interaction with Tyrosine, higher dock scores, and better stability than Diclofenac. Following the synthesis of hit molecules, an in vitro albumin denaturation IC50 of Dh1 was found to be 118.01µM. Further in-depth in vitro and in vivo analyses of these pyrazole-pyridine small compounds may serve as potential space for creating new anti-inflammatory leads.

Visual Eosin Y-Based Photosensitization Sensing Systems for Ultrasensitive Detection of Diclofenac with Single-Atom Co─N2O2 Site-Immobilized g-C3N4 Nanosheets.

It is highly desired to develop a visual sensing system for ultrasensitive detection of colorless diclofenac (DCF), yet with a significant challenge. Herein, a novel dye-based photosensitization sensing system has been successfully developed for detecting DCF for the first time, in which the used dye eosin Y (DeY) can strongly absorb visible light and then be decolorized obviously by transferring photogenerated electrons to g-C3N4 nanosheets (CN), while the built single-atomic Co─N2O2 sites on CN by boron-oxygen connection can competitively adsorb DCF to impede the photosensitization decoloration of DeY. This system exhibits a broad detection range from 8 ng L-1 to 2 mg L-1 with 535 nm light, an exceptionally low detection limit (3.5 ng L-1), and remarkable selectivity. Through the time-resolved, in situ technologies, and theoretical calculations, the decolorization of DeY is attributed to the disruption of DeY's conjugated structure caused by the triplet excited state electron transfer from DeY to CN, meanwhile, the adsorbed oxygen facilitates the charge transfer process. The preferential adsorption of DCF mainly depends on the strong interactions between the as-constructed single-atom Co and Cl in DCF. This study opens an innovative light-driven sensing system by combining dye and single-atom metal/nanomaterial for visually intuitive detection of environmental pollutants.

Development of an RP-HPLC Method for Quantifying Diclofenac Diethylamine, Methyl Salicylate, and Capsaicin in Pharmaceutical Formulation and Skin Samples.

An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical formulation and rabbit skin samples. The separation was achieved using a Thermo Scientific ACCLAIMTM 120 C18 column (Waltham, MA, USA, 4.6 mm × 150 mm, 5 µm). The optimized elution phase consisted of deionized water adjusted to pH = 3 using phosphoric acid mixed with acetonitrile in a 35:65% (v/v) ratio with isocratic elution. The flow rate was set at 0.7 mL/min, and the detection was performed at 205 nm and 25 °C. The method exhibits good linearity for capsaicin (0.05-70.0 µg/mL), methyl salicylate (0.05-100.0 µg/mL), and diclofenac diethylamine (0.05-100.0 µg/mL), with low LOD values (0.0249, 0.0271, and 0.0038 for capsaicin, methyl salicylate, and diclofenac diethylamine, respectively). The RSD% values were below 3.0%, indicating good precision. The overall greenness score of the method was 0.61, reflecting its environmentally friendly nature. The developed RP-HPLC method was successfully applied to analyze Omni Hot Gel® pharmaceutical formulation and rabbit skin permeation samples.

Fabrication and optimization of extended-release beads of diclofenac sodium based on Ca++ cross-linked Taro (Colocasia esculenta) stolon polysaccharide and pectin by quality-by-design approach.

The present investigation was aimed to fabricate and optimize extended-release beads of diclofenac sodium based on an ion-cross-linked matrix of pectin (PTN) and taro (Colocasia esculenta) stolon polysaccharide (TSP) with 23 full factorial design. Total polysaccharide concentration (TPC), polysaccharide ratio (PR), and cross-linker concentration ([CaCl2]) were taken as independent factors with two levels of each. Initially, TSP was extracted, purified, and characterized. Fourier-transform infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed drug-polymer compatibility. The study also revealed the significant positive effect of TSP on drug entrapment efficiency (DEE) and sustaining drug release. The response variables (DEE, cumulative % drug-release at 1, 2, 4, 6, and 10 h, release-constant, time for 50 % and 90 % drug release (T50%, T90%), release-similarity factor (f2), and difference factor (f1) were analyzed, and subsequently, independent fabrication variables were numerically optimized by Design-Expert software (Version-13; Stat-Ease Inc., Minneapolis). The optimized batch exhibited appreciable DEE of 88.5 % (± 2.2) and an extended-release profile with significantly higher T50%, T90%, and release-similarity factor (f2) of 4.7 h, 11.4 h, and 71.6, respectively. Therefore, the study exhibited successful incorporation of the novel TSP as a potential alternative adjunct polysaccharide in the pectin-based ion-cross-linked inter-penetrating polymeric network for extended drug release.

Adsorption studies of tetracycline hydrochloride and diclofenac sodium on NH2-MIL-53(Al/Zr) sodium alginate gel spheres.

Metal-organic frameworks are emerging inorganic-organic hybrid materials that can be self-assembled from metal ions and organic ligands via coordination bonds. These materials possess large specific surface area, tunable pore structure, abundant active center, diversity of functional groups as well as high mechanical and thermal stability which promote their applications in adsorption and catalysis studies. In this study, NH2-MIL-53(Al/Zr) was prepared and embedded into sodium alginate gel spheres (NH2-MIL-53(Al/Zr)-SA) and its adsorption properties towards TC and DCF in solution were investigated. According to XRD and FTIR analysis, the structure of the raw material was not changed after making the gel spheres. The maximum adsorption towards TC (pH =3) and DCF (pH =5) reached 98.5 mg·g-1 and 192 mg·g-1, respectively. The process was consistent with Langmuir and Freundlich, suggesting that there was both monolayer and multilayer adsorption which infers the presence of physical adsorption (intra-particle diffusion) and non-homogeneous chemical adsorption. The thermodynamic parameters showed that the adsorption process was a spontaneous entropy increasing reaction. The regeneration rate of spent NH2-MIL-53(Al/Zr)-SA could still reach 99.1 % after three cycles, indicating good regeneration performance. This study can provide a basis for the application of NH2-MIL-53(Al/Zr)-SA in wastewater treatment.

Diclofenac sodium nanomedicine results in pain-relief and differential expression of the RNA transcriptome in the spinal cord of SNI rats.

Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation.

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.

Effects of Ibuprofen and Diclofenac Pre-Treatment on Viability and Apoptosis Processes in Human Dental Pulp Stem Cells.

Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.