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Journal of Nanobiotechnology Oct 2020Magnetic nanocomposites with a core-shell nanostructure have huge applications in different sciences especially in the release of the drugs, because of their exclusive...
BACKGROUND
Magnetic nanocomposites with a core-shell nanostructure have huge applications in different sciences especially in the release of the drugs, because of their exclusive physical and chemical properties. In this research, magnetic@layered double hydroxide multicore@shell nanostructure was synthesized by the facile experiment and is used as novel drug nanocarrier.
METHODS
Magnetic nanospheres were synthesized by a facile one-step solvothermal route, and then, layered double hydroxide nanoflakes were prepared on the magnetic nanospheres by coprecipitation experiment. The synthesized nanostructures were characterized by FTIR, XRD, SEM, VSM, and TEM, respectively. After intercalation with Ibuprofen and Diclofenac as anti-inflammatory drugs and using exchange anion experiment, the basal spacing of synthesized layered double hydroxides was compared with brucite nanosheets from 0.48 nm to 2.62 nm and 2.22 nm, respectively.
RESULTS
The results indicated that Ibuprofen and Diclofenac were successfully intercalated into the interlay space of LDHs via bridging bidentate interaction. In addition, in-vitro drug release experiments in pH 7.4, phosphate-buffered saline (PBS) showed constant release profiles with Ibuprofen and Diclofenac as model drugs with different lipophilicity, water solubility, size, and steric effect.
CONCLUSION
The FeO@LDH-ibuprofen and FeO@LDH-diclofenac had the advantage of the strong interaction between the carboxyl groups with higher trivalent cations by bridging bidentate, clarity, and high thermal stability. It is confirmed that FeO@LDH multicore-shell nanostructure may have potential application for constant drug delivery.
Topics: Animals; Anti-Inflammatory Agents; Delayed-Action Preparations; Diclofenac; Drug Carriers; Drug Compounding; Drug Liberation; Humans; Hydroxides; Ibuprofen; Intercalating Agents; Magnetic Iron Oxide Nanoparticles; Mice; Myoblasts; Nanocomposites; Particle Size; Solubility; Surface Properties
PubMed: 33121499
DOI: 10.1186/s12951-020-00718-y -
Journal of the American Veterinary... Jul 2024To investigate systemic absorption and gastrointestinal (GI) adverse effects of topical ketorolac 0.5% and diclofenac 0.1% ophthalmic solutions.
OBJECTIVE
To investigate systemic absorption and gastrointestinal (GI) adverse effects of topical ketorolac 0.5% and diclofenac 0.1% ophthalmic solutions.
ANIMALS
11 healthy purpose-bred Beagles.
METHODS
Dogs were randomly assigned to receive either ketorolac (n = 6) or diclofenac (5), 1 drop in both eyes 4 times daily for 28 days. Upper GI endoscopy was performed on days 0 and 29 with mucosal lesion scores (0 to 7) assigned to each region evaluated. Plasma samples were collected on days 14, 21, and 28 for measurement of diclofenac and ketorolac using high-performance liquid chromatography-mass spectrometry.
RESULTS
GI erosions and/or ulcers developed in all ketorolac-treated dogs and 1 of 5 diclofenac-treated dogs. Post-treatment mucosal lesion score for the antrum was higher in the ketorolac group than in the diclofenac group (P = .006) but not significantly different for any other region. Post-treatment antral mucosal lesion scores were significantly related to plasma ketorolac concentrations (P < .001). Ketorolac and diclofenac were detected in the plasma at all time points (median ketorolac day 14, 191 ng/mL; day 21, 173.5 ng/mL; and day 28, 179.5 ng/mL; and median diclofenac day 14, 21.1 ng/mL; day 21, 20.6 ng/mL; day 28, 27.5 ng/mL). Vomiting and decreased appetite events were observed uncommonly and were not significantly different between treatment groups.
CLINICAL RELEVANCE
GI ulceration and erosion developed after ophthalmic administration of ketorolac and diclofenac, with higher plasma concentrations and more severe GI lesions associated with ketorolac. Clients should be alerted to this potential risk with ophthalmic use and informed to watch for systemic clinical signs that would warrant veterinary reevaluation.
Topics: Animals; Dogs; Diclofenac; Anti-Inflammatory Agents, Non-Steroidal; Ketorolac; Ophthalmic Solutions; Male; Female; Dog Diseases; Administration, Topical; Gastrointestinal Diseases
PubMed: 38579753
DOI: 10.2460/javma.23.12.0707 -
Archives of Razi Institute Apr 2022The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in...
The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in metabolisms, detoxifications, storage, elimination of medications, and their metabolites. The present study aimed to examine the role of the natural and free radical scavenger "CoQ10" against diclofenac-induced hepatic and renal tissue injury. In total, 36 adult Wistar rats were randomly divided into three equal groups (n=12). The animals in the control group did not receive any medication or treatments, and the second group included animals that received intramuscular (IM) injection of Diclofenac (DF) (at a dose of 10 mg/kg once daily for 14 days). Moreover, the third group was given the IM injection of DF (at a dose of 10 mg/kg once daily for 14 days) +CoQ10. After 14 days, DF prompted signified hepatic and renal injury indicated by elevated biochemical parameters, such as total serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, and uric acid, compared to the control and the third group. However, the group that received Diclofenac+CoQ10 had significantly lower hepatic and renal dysfunctions, compared to the second treated group. DF toxic effects could be the consequences of mitochondrial dysfunction and free radical effects. Remarkably, therapeutic supplementation of CoQ10 diminished the DF-induced toxic oxidative injury and apoptotic cell death. The protective effects of CoQ10 were attributed to its antioxidants and free radical scavenger activity.
Topics: Rats; Animals; Diclofenac; Alanine Transaminase; Free Radical Scavengers; Creatinine; Uric Acid; Alkaline Phosphatase; Rats, Wistar; Aspartate Aminotransferases; Bilirubin
PubMed: 36284948
DOI: 10.22092/ARI.2022.357210.1998 -
Biomolecules Oct 2019This paper reported the first example on the use of chitosan films, without further modification, to remove and recover, through bio-sorption processes, the emerging...
This paper reported the first example on the use of chitosan films, without further modification, to remove and recover, through bio-sorption processes, the emerging pollutant Diclofenac from water. The latter was adopted as a model, among non-steroidal anti-inflammatory drugs, by obtaining a maximum adsorption capacity, q, on chitosan of about 10 mg/g, under the applied experimental conditions of work. The literature gap about the use of chitosan films, which was already used for dyes and heavy metals removal, to adsorb emerging pollutants from water was covered, claiming the wide range application of chitosan films to remove a different class of pollutants. Several parameters affecting the Diclofenac adsorption process, such as the pH and ionic strength of solutions containing Diclofenac, the amount of the bio-sorbent and pollutant, and the temperature values, were investigated. The kinetics and the adsorption isotherms, along with the thermodynamic parameters (ΔG°, ΔH°, and ΔS°) were also evaluated. The process occurred very efficiently, and Chitosan/Diclofenac amounts dependent, remove about the 90% of the pollutant, in 2 h, from the tested solutions, through electrostatic interaction involving the carboxylic moiety of Diclofenac and Chitosan amino groups. This finding was confirmed by the pH and salt effects on the bio-sorption process, including swelling measurements of Chitosan films and by FTIR-ATR analysis. In detail, the maximum adsorption was observed at pH 5, when pollutant and Chitosan were negatively and positively charged, respectively. By reducing or increasing the pH around this value, a reduced affinity was observed. Accordingly, the presence of salts retarded the Diclofenac removal screening its charges, which hinders the interaction with Chitosan. The sorption was spontaneous (ΔG° < 0) and endothermic (ΔH° > 0) following the pseudo-second order kinetic model. The process was Diclofenac and Chitosan amount dependent. In addition, the Freundlich and Temkin isotherms well described the process, which showed the heterogeneous character of the process. Experiments of the complete desorption were also performed by using NaCl solutions 0.25 M (like sea water salt concentration) proposing the reuse of the pollutant and the recycling of the bio-sorbent lowering the associated costs. The versatility of the adsorbent was reported by exploring the possibility to induce the Diclofenac light-induced degradation after the adsorption and by-products adsorption onto chitosan films. To emphasize the chitosan capacity of treating water, the removal of another pollutant such as Ketoprofen and the mixture of Diclofenac and Ketoprofen were investigated. In this way, a green and eco-friendly production-pollution prevention technology for removing emerging pollutants from water was presented, which reduced the overall environmental impact. This illustrated experiments both in static and dynamic conditions for potential industrial applications.
Topics: Adsorption; Chitosan; Diclofenac; Hydrogen-Ion Concentration; Industrial Waste; Ketoprofen; Spectroscopy, Fourier Transform Infrared; Wastewater; Water Purification
PubMed: 31590344
DOI: 10.3390/biom9100571 -
Redox Biology Oct 2020Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest...
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest that mitochondrial damage and oxidative stress are important mediators of toxicity, yet the underlying mechanisms are poorly understood. In this study, we identified that some NSAIDs, including diclofenac, inhibit autophagic flux in hepatocytes. Further detailed studies demonstrated that diclofenac induced a reactive oxygen species (ROS)-dependent increase in lysosomal pH, attenuated cathepsin activity and blocked autophagosome-lysosome fusion. The reactivation of lysosomal function by treatment with clioquinol or transfection with the transcription factor EB restored lysosomal pH and thus autophagic flux. The production of mitochondrial ROS is critical for this process since scavenging ROS reversed lysosomal dysfunction and activated autophagic flux. The compromised lysosomal activity induced by diclofenac also inhibited the fusion with and degradation of mitochondria by mitophagy. Diclofenac-induced cell death and hepatotoxicity were effectively protected by rapamycin. Thus, we demonstrated that diclofenac induces the intracellular ROS production and lysosomal dysfunction that lead to the suppression of autophagy. Impaired autophagy fails to maintain mitochondrial integrity and aggravates the cellular ROS burden, which leads to diclofenac-induced hepatotoxicity.
Topics: Autophagy; Chemical and Drug Induced Liver Injury; Diclofenac; Humans; Lysosomes; Oxidative Stress; Reactive Oxygen Species
PubMed: 33080439
DOI: 10.1016/j.redox.2020.101751 -
Turkish Journal of Medical Sciences Oct 2022In this study, we evaluate sciatic nerve injuries due to intramuscular injections, which is an important medicolegal problem frequently encountered in medical practice,...
BACKGROUND
In this study, we evaluate sciatic nerve injuries due to intramuscular injections, which is an important medicolegal problem frequently encountered in medical practice, with an extended experimental rat model of peripheral nerve injury.
METHODS
A total of 78 male Wistar albino rats were divided into five main groups, including a control group, a sham saline group, and groups that received benzathine penicillin G, diclofenac sodium, and dexamethasone, respectively. These pharmaceutical agents were applied to the sciatic nerves of all rats after exploration in the epineurial, endoneurial, and intrafascicular compartments, excluding the control group. Outcomes were evaluated for all rats and their sciatic nerves according to functional, electrophysiological, and histopathological results.
RESULTS
Injuries were most evident in the groups that received penicillin G and diclofenac sodium, and this finding was statistically significant. It was also found that endoneurial and intrafascicular injections may cause more harm than epineurial injections.
DISCUSSION
We have demonstrated that any medical injections applied to the epineurial, endoneurial, or intrafascicular compartments of the sciatic nerve may cause functional and electrophysiological loss with or without deterioration of the peripheral nerve architecture.
Topics: Male; Rats; Animals; Rats, Wistar; Peripheral Nerve Injuries; Diclofenac; Sciatic Nerve; Injections, Intramuscular
PubMed: 36422486
DOI: 10.55730/1300-0144.5499 -
Journal of Inorganic Biochemistry Dec 2023The recently isolated Sclerotinia sclerotiorum laccase was used for the degradation of sodium diclofenac, a nonsteroidal anti-inflammatory drug widely found in the...
The recently isolated Sclerotinia sclerotiorum laccase was used for the degradation of sodium diclofenac, a nonsteroidal anti-inflammatory drug widely found in the aquatic environment. The Michaelis-Menten parameters, half-life of diclofenac at different pH values in presence of this enzyme and potential inhibitors were evaluated. Diclofenac-based radicals formed in presence of laccase were spin-trapped and detected using EPR spectroscopy. Almost complete diclofenac degradation (> 96%) occurred after a 30-h treatment via radical-based generated oligomers and their rapid precipitation, thus ensuring an unprecedented green formula suitable not only for degradation but also for straightforward removal of the degradation products. High performance liquid chromatography coupled with atmospheric pressure chemical ionization-ion trap mass spectrometry (HPLC-APCI-MS) analyses of the degradation products of diclofenac in aqueous dosage revealed the presence of at least seven products while HR Orbitrap MS analysis showed that the enzymatic treatment produced high molecular weight metabolites through a radical oligomerization mechanism of diclofenac. The enzymatically formed products precipitated and its constituting components were also characterized using UV-vis spectroscopy, infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA).
Topics: Diclofenac; Laccase; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid
PubMed: 37844532
DOI: 10.1016/j.jinorgbio.2023.112400 -
Scientific Reports Sep 2023The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a...
The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer's disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1-42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.
Topics: Humans; Diclofenac; Amyloidogenic Proteins; Amyloidosis; Prostaglandin-Endoperoxide Synthases; Immunoglobulin Light-chain Amyloidosis
PubMed: 37660155
DOI: 10.1038/s41598-023-41712-2 -
PeerJ 2023Amultigenerational study on was carried out by exposing three subsequent generations to pharmaceuticals chlorpromazine (CPZ) and diclofenac (DCF), and two lanthanide...
Amultigenerational study on was carried out by exposing three subsequent generations to pharmaceuticals chlorpromazine (CPZ) and diclofenac (DCF), and two lanthanide chlorides, gadolinium as GdCl and europium as EuCl. As the treatments, environmentally relevant concentrations were chosen (0.001, 0.01 and 0.1 mg/L for CPZ; 0.1, 1 and 10 mg/L for DCF; 0.425, 4.25 and 42.5 µg/L for Gd and 0.41, 4.1 and 41 µg/L for Eu). Survival, population growth and reproduction success were evaluated at 21 and 30 days of exposure, and the whole observation period lasted 40 days. The least sensitive to all selected substances was the first daphnid generation (F1). Within 21-day exposure, no significant effects of the psychotropic drug CPZ on survival were observed in generations F1-F3. The anti-inflammatory drug DCF did not affect survival in the F1 generation; however, it significantly reduced survival in the F3 generation at 1-10 mg/L. Both lanthanides did not affect survival in the F1 and F2 generations of but considerably decreased survival in the F3 at 4-42 µg/L. Both pharmaceuticals stimulated the reproduction of in the F1 generation, while inhibition occurred at the highest tested concentrations in generations F2 and F3. The inhibitory effect on the reproductive success of lanthanides in the F2 generation resembled that for CPZ but not for DCF. The dynamics of adverse effects during the 21-30-day period revealed that despite increased mortality in the controls (up to 30%), concentrations used in the study minified, in most instances, the survival and aggravated population growth and reproduction success of . Our data suggest that as a test organism can be used for 21 days in multigenerational investigations, especially when testing close to environmental concentrations. In this respect, the standard chronic toxicity assay seems limited since prolonged observations and several generations of daphnids are required to obtain reliable information for the risk assessment of potentially aggressive chemicals.
Topics: Animals; Chlorpromazine; Cladocera; Diclofenac; Lanthanoid Series Elements
PubMed: 38025671
DOI: 10.7717/peerj.16472 -
Clinical Drug Investigation Jan 2022A topical formulation of diclofenac (FLECTOR diclofenac epolamine topical system (FDETS)) is approved in adults for the treatment of acute pain due to minor strains,...
BACKGROUND AND OBJECTIVE
A topical formulation of diclofenac (FLECTOR diclofenac epolamine topical system (FDETS)) is approved in adults for the treatment of acute pain due to minor strains, sprains, and contusions; however, its safety and efficacy have not been investigated in a pediatric population. This study assessed the safety and efficacy of the FLECTOR (diclofenac epolamine) topical system in children.
METHODS
This was an open-label, single-arm, phase IV study at ten USA-based family medicine or pediatric practices in children aged 6-16 years with a clinically significant minor soft tissue injury sustained within the preceding 96 h and at least moderate spontaneous pain on the Wong-Baker FACES Pain Rating Scale. The FLECTOR topical system was applied twice daily until pain resolution or Day 14. The primary endpoint was local tolerability and systemic safety. Key secondary endpoints were diclofenac plasma concentrations and analgesic efficacy.
RESULTS
104 patients were enrolled; 52 were 6-11 years old, and 52 were 12-16 years old (mean age 11.6 years). The maximum tolerability score experienced by any patient was 1 (faint redness). Fourteen adverse events (none serious) in nine patients (8.7%) were considered possibly treatment-related. Reduction in pain during the study was somewhat greater for patients aged 6-11 versus 12-16 years (p < 0.011). The diclofenac plasma concentration tended to be higher in the younger age group compared with older patients: 1.83 versus 1.46 ng/mL at the first assessment and 2.49 versus 1.11 ng/mL at the last assessment (p = 0.002).
CONCLUSION
The FLECTOR topical system safely and effectively provided pain relief for minor soft tissue injuries in the pediatric population, with minimal systemic nonsteroidal anti-inflammatory drug exposure and low potential risk of local or systemic adverse events.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02132247.
Topics: Acute Pain; Administration, Topical; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Diclofenac; Humans; Pyrrolidines; Soft Tissue Injuries
PubMed: 34826122
DOI: 10.1007/s40261-021-01101-x