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Possible and known applications of diclofenac. Diclofenac can act as an analgesic agent by activating transient outward potassium channels in neurons and simultaneously reducing the production of prostaglandins. Diclofenac can also act as a potent inhibitor of oligomerization of β-amyloid fibrils and plaque formation, which can be used in the development of therapies for diseases involving amyloid aggregation. Alternatively, diclofenac also interferes with the activation of glial cells, which may further contribute to its neuroprotective properties. Diclofenac has both inhibitory and inducing effects on cell death under different conditions. Endoplasmic reticulum stress generated by thapsigargin leads to activation of caspases and causes mitochondrial depolarization. Diclofenac suppresses the intrinsic pathway of apoptosis by interfering with caspase activation and
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Diclofenac is a highly prescribed non-steroidal anti-inflammatory drug (NSAID) that relieves inflammation, pain, fever, and aches, used at different doses depending on clinical conditions. This drug inhibits cyclooxygenase-1 and cyclooxygenase-2 enzymes, which are responsible for the generation of prostaglandin synthesis. To improve current diclofe...
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... an experimental focal penetrating traumatic brain injury in rats, the COX-2 inhibition-mediated protective effect of diclofenac appeared to be involved in reduced apoptosis and wound area [107]. Figure 3 provides a schema of various mechanisms involved in diclofenac-mediated protective effects. production of prostaglandins. ...
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... studies have suggested both pro-and anti-apoptotic effects of diclofenac [72,108,109]. As depicted in Figure 3, diclofenac alleviates apoptosis induced by thapsigargin-induced endoplasmic reticulum stress conditions [110]. Moreover, the suppression of caspase activity by diclofenac was due to the inhibitory effect of diclofenac on mitochondrial depolarization, and subsequently, on apoptosis [110]. ...
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... the suppression of caspase activity by diclofenac was due to the inhibitory effect of diclofenac on mitochondrial depolarization, and subsequently, on apoptosis [110]. Interestingly, various pathways of diclofenac inducing apoptosis and inhibiting proliferation of cancer cells have also been reported, as shown in Figure 3, indicating its dual role. These mechanisms include inhibition of proteasomes [72], enhancement of ROS production [111], increase in p73 activity [112], and inhibition of MYC expression and lactate transport [19]. ...
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Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be further elucidated. Using the mouse model, we showed...
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... Currently, on the market, the most popular trade names are Algosenac, Almiral, Diclomex, Dicuno, Voltaren. Diclofenac is also used to treat epilepsy, autoimmune conditions, and acute pancreatitis (Amanullah et al., 2022). Due to its excessive use in human and veterinary fields, it has been among the most detected substances in the environment since 2000. ...
Drugs are chemical compounds used to treat and improve organic dysfunctions caused by diseases. These include analgesics, antibiotics, antidepressants, and antineoplastics. They can enter aquatic environments through wastewater streams, where their physico-chemical properties allow metabolites to distribute and accumulate. Current climate change and associated extreme weather events may significantly impact these substances' toxicity and aquatic organisms' sensitivity. Among the chemicals present in aquatic environments is the non-steroidal anti-inflammatory drug diclofenac (DIC), which the EU monitors due to its concentration levels. This study investigated the influence of temperature (control at 17 °C vs. 21 °C) on the effects of DIC (0 μg/L vs. 1 μg/L) in the mussel species Mytilus galloprovincialis. Significant results were observed between 17 and 21 °C. Organisms exposed to the higher temperature showed a decrease in several parameters, including metabolic capacity and detoxification, particularly with prolonged exposure. However, in some parameters, after 21 days, the M. galloprovincialis showed no differences from the control, indicating adaptation to the stress. The results of this study confirm that DIC concentrations in the environment, particularly when combined with increased temperatures, can produce oxidative stress and adversely affect M. galloprovincialis biochemical and physiological performance. This study also validates this species as a bioindicator for assessing environmental contamination with DIC. Beyond its direct impact on aquatic organisms, the presence of pharmaceuticals like DIC in the environment highlights the interconnectedness of human, animal, and ecosystem health, underscoring the One Health approach to understanding and mitigating environmental pollution.
... This change in the ratio of these substances helps to slow down the secretion of anti-inflammatory factors [12,13]. A reduction in the release of free oxygen radicals, which occurs under the influence of diclofenac sodium, can also contribute to a decrease in the inflammatory process activity [14]. In addition to pronounced anti-inflammatory activity, diclofenac sodium has complex effects on various mechanisms of pain perception, providing effective suppression of pain syndromes of various aetiologies, as well as central and peripheral antinociceptive effects [15,16]. ...
The formulation of biphasic gels as potential semi-solid carriers for hydrophilic and lipophilic active substances is promising for the development of pharmaceutical preparations. The aim of this study was to design a stable bigel composition and to determine the influence of the organogel/hydrogel ratio on the gel’s physical-chemical and structural-mechanical properties. The investigated compositions of organogel/hydrogel remained stable at ratios ranging from 5/95 to 40/60. After texture and microstructure analysis, bigels with 20/80 and 25/75 ratios were selected as carriers for the active ingredients, sodium diclofenac and camphor, for use as topical preparations for the treatment of muscle-joint inflammation and pain. Although other researchers have published data on the preparation and evaluation of bigels, there are no scientific results on the development of a two-phase gel with our proposed combination of APIs. Sodium diclofenac release was found to be higher when combined with camphor, which revealed the advantages of the biphasic formulation. The pseudoplastic behavior, thixotropy, and thermal stability of flow of the studied bigel samples was investigated by rheological analysis. Ongoing stability studies confirmed the minimal 6-month period.
... Until now, the cytotoxic activity of progestins, glucocorticoids, and diclofenac has not yet been evaluated on Hep-2 and K-562 cancer cell lines. There is no information about the IC 50 values for progestins and glucocorticoids, which could add to knowledge of the pharmacological activity of these hormones and expand their indications for use, since the repurposing of drugs, in particular diclofenac [29], has become a frequent occurrence. ...
... Some well-known NSAIDs are already being repurposed: they can be used not only in the treatment of cancer-related pain but also as anticancer drugs and chemosensitizing drugs [24,41,51]. The cytotoxic action of NSAIDs is realized via different mechanisms: a decrease in the expression of MYC (a family of regulator genes and protooncogenes that code for transcription factors), the regeneration of intracellular ROS and induction of apoptotic death, cell cycle arrest at different checkpoints, the inhibition of cell proliferation and migration, activating autophagy, and microtubule destabilization [29,52]. DCF also sensitizes cancerous cells to cisplatin and 5-fluorouracil [41,52]. ...
A comparative analysis of the cytostatic effects of progestins (gestobutanoyl, megestrol acetate, amol, dienogest, and medroxyprogesterone acetate), glucocorticoids (hydrocortisone, dexamethasone), and diclofenac on tumor cells was carried out in order to confirm their in silico predicted probabilities experimentally. The results showed the different sensitivity of HeLa, MCF-7, Hep-2, K-562, and Wi-38 cell lines to progestins, glucocorticoids, and diclofenac. The minimum IC50 was found for progestin gestobutanoyl (GB) as 18 µM for HeLa cells, and varied from 31 to 38 µM for MCF-7, Hep-2, and K-562. Glucocorticoids and diclofenac were much less cytotoxic in the HeLa, MCF-7, and Hep-2 cell lines than progestins, with IC50 values in the range of 150–3000 μM. Myelogenous leukemia K-562 cells were the least sensitive to the action of progestins and glucocorticoids but the most sensitive to diclofenac, which showed a pronounced cytotoxic effect with an IC50 of 31 μM. As we have shown earlier, progestins can uniquely modulate MPTP opening via the binding of adenine nucleotide translocase. On this basis, we evaluated the expression of adenylate nucleotide translocase ANT1 (SLC25 A4) as a possible participant in cytotoxic action in these cell lines after 48 h incubation with drugs. The results showed that progestins differently regulated ANT1 expression in different cell lines. Gestobutanoyl had the opposite effect on ANT1 expression in the HeLa, K562, and Wi-38 cells compared with the other progestins. It increased the ANT1 expression more than twofold in the HeLa and K562 cells but had no influence on the Wi-38 cells. Glucocorticoids and diclofenac increased ANT1 expression in the Wi-38 cells and decreased it in the K562, MCF-7, and Hep-2 cells. The modulation of ANT1 expression discovered in our study can be a new explanation of the cytotoxic and cytoprotective effects of hormones, which can vary depending on the cell type. ANT isoforms in normal and cancerous cells could be a new target for steroid hormone and anti-inflammatory drug action.
... After oral administration, the bioavailability of the drug and its plasma half-life are approximately 50-60% and 1-2 h, respectively [39]. The necessity for multiple daily doses of this medication can lead to adverse outcomes, including gastrointestinal upset, increased risk of cardiovascular events, drug-induced hepatic damage, or diarrhea [40]. Hence, our study aimed to optimize the synthesis of non-toxic Fe-based metal-organic frameworks, MIL-88A, with divergent morphologies and their application as carriers in the diclofenac sodium release at the medium reflecting intestinal condition (pH 6.8). ...
... After oral administration, the bioavailability of drug and its plasma half-life are approximately 50-60% and 1-2 h, respectively [39]. T necessity for multiple daily doses of this medication can lead to adverse outcomes, inclu ing gastrointestinal upset, increased risk of cardiovascular events, drug-induced hepa damage, or diarrhea [40]. Hence, our study aimed to optimize the synthesis of non-to Fe-based metal-organic frameworks, MIL-88A, with divergent morphologies and th application as carriers in the diclofenac sodium release at the medium reflecting intesti condition (pH 6.8). ...
Migraine is now the sixth most common disease in the world and affects approximately 15% of the population. Non-steroidal anti-inflammatory drugs, including ketoprofen, diclofenac sodium, and ibuprofen, are often used during migraine attacks. Unfortunately, their efficiency can be reduced due to poor water solubility and low cellular uptake. This requires the design of appropriate porous carriers, which enable drugs to reach the target site, increase their dissolution and stability, and contribute to a time-dependent specific release mode. In this research, the potential of the MIL-88A metal-organic frameworks with divergent morphologies as diclofenac sodium delivery platforms was demonstrated. Materials were synthesized under different conditions (temperature: 70 and 120 °C; solvent: distilled water or N,N-Dimethylformamide) and characterized using X-ray diffraction, low-temperature nitrogen adsorption/desorption, thermogravimetric analysis, infrared spectroscopy, and scanning electron microscopy. They showed spherical, rod- or diamond-like morphologies influenced by preparation factors. Depending on physicochemical properties, the MIL-88A samples exhibited various sorption capacities toward diclofenac sodium (833–2021 mg/g). Drug adsorption onto the surface of MIL-88A materials primarily relied on the formation of hydrogen bonds, metal coordination, and electrostatic interactions. An in vitro drug release experiment performed at pH 6.8 revealed that diclofenac sodium diffused to phosphate buffer in a controlled manner. The MIL-88A carriers provide a high percentage release of drug in the range of 58–97% after 24 h.
... Multiple, mechanisms [422] Improved disease free survival in breast cancer surgery [423]. Normalizes skin lesions when applied topically [424]. ...
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be effected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention, and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
... DFS inhibit working of cyclooxygenase-I and cyclooxygenase-II enzymes thus, decreases production of prostaglandins that cause pains [36]. Subsequently, it is used in management of ulcers, dental pains, cancerous pains, painful periods and surgical pains [37][38][39][40]. In addition, DFS is also administered to deal with inflammatory disorders such as arthritis, muscular sprains, actinic keratosis gout, osteoarthritis, rheumatoid arthritis and spondylitis [41]. ...
In the current study, hydrogels for the controlled release of diclofenac sodium were synthesized from graphene oxide-reinforced guar gum and poly (N-vinyl-2-pyrrolidone) using the Solution Casting Technique. Varying concentrations of 3-Glycidyloxypropyl trimethoxysilane (GLYMO) were employed for the crosslinking of hydrogels. Further, the characterization of hydrogels was carried out using different techniques such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction, thermal analysis and scanning electron microscope. The FTIR investigations reveals particular functionalities and development of hydrogel interfaces. While thermal analysis prophesied that, improvement in forces among hydrogel components is directly proportional to the GLYMO concentration. In-vitro biodegradation test and cell viability assay against HEK-293 cell lines confirmed their biodegradable and biocompatible nature. GPG-32 demonstrated maximum antibacterial activity against P.aeruginosa and E.coli strains. The maximum swelling 2001 % and 1814 % in distilled water were recorded for GPG (control) and GPG-8 respectively that obeyed Fick's law. Hydrogels displayed high swelling responses at pH 6 in buffer and non-buffer solutions. In 2.5 h, 88.7 % diclofenac sodium was released which was determined by UV visible spectrophotometer. In conclusion, guar gum-based non-toxic, biocompatible and biodegradable hydrogels would be a model platform for targeting inflammation and pains. Furthermore, improved mechanical and viscoelastic behavior of hydrogels could also be explored for making drug loaded dressings for wound healing applications.
... In this work, we explored a CHT/VCO-based emulsion system to create 3D architectures using a freeze-drying technique and the incorporation of cubosomes loaded with sodium diclofenac to develop a drug-delivery system. For this purpose, phytantriol cubosomes (Cub) were prepared with sodium diclofenac (SD), a non-steroidal anti-inflammatory drug that is frequently used to treat inflammatory diseases [26,27], and were chosen as a model drug. With this proposed approach, we hypothesized that the CHT/VCO-based system would provide controlled release properties, while protecting the cubosomes from degradation. ...
Emulsion-based systems that combine natural polymers with vegetable oils have been identified as a promising research avenue for developing structures with potential for biomedical applications. Herein, chitosan (CHT), a natural polymer, and virgin coconut oil (VCO), a resource obtained from coconut kernels, were combined to create an emulsion system. Phytantriol-based cubosomes encapsulating sodium diclofenac, an anti-inflammatory drug, were further dispersed into CHT/VCO- based emulsion. Then, the emulsions were frozen and freeze-dried to produce scaffolds. The scaffolds had a porous structure ranging from 20.4 to 73.4 µm, a high swelling ability (up to 900%) in PBS, and adequate stiffness, notably in the presence of cubosomes. Moreover, a well-sustained release of the entrapped diclofenac in the cubosomes into the CHT/VCO-based system, with an accumulated release of 45 ± 2%, was confirmed in PBS, compared to free diclofenac dispersed (80 ± 4%) into CHT/VCO-based structures. Overall, the present approach opens up new avenues for designing porous biomaterials for drug delivery through a sustainable pathway.
... DCF can be administered orally or applied to the skin (Leppert et al. 2018). Headache, renal and hepatic damage, skin rashes, gastrointestinal lesions, edema and dizziness are the reported side effects of DCF (Amanullah et al. 2022). Municipal waste, effluent discharge from hospitals, pharmaceutical units and wastewater treatment plants (WWTPs) are the most prominent sources of diclofenac in the aquatic environment (Alessandretti et al. 2021;Osorio et al. 2016). ...
The annual growth rate of pharmaceutical industry in Pakistan is 10% and is continuously expanding to fulfill the increasing demand of the rapidly growing population. But inability of the pharmaceutical sector to comply with the environmental standards leads to the introduction of large quantities of various pollutants in the natural environment which presents serious ecological challenges. In this study, effluent wastewater samples from 14 manufacturing units of the pharmaceutical industries of the National Industrial Zone, Rawat, Pakistan, were collected and characterized for physicochemical parameters including color, odor, pH, electric conductivity, temperature, total dissolved solids, total suspended solids, salinity, dissolved oxygen (DO), chemical oxygen demand (COD), nitrates, sulfates and phosphates according to the standard methods. The detection and quantification of diclofenac (DCF)—one of the commonly prescribed drugs in Pakistan—were carried out in the pharmaceutical wastewater samples (PWWSs) using HPLC-PAD. Exceptionally high concentration of the diclofenac was detected in the industrial disposal of MB-12 ( 311,495 µg L ⁻¹ ) . PWWSs were analyzed using chemometric techniques including principal factor analysis (PFA) and cluster analysis (CA). PFA explained almost 81.48% of the total variance by the newly extracted four components and complemented the strong Pearson’s correlation coefficient ( r ) of DCF concentrations to that of the levels of COD, r = 0.752, and DO, r = − 0.609, in PWWSs. Six clusters were generated during similar wastewater characteristics-based CA dendrogram, in which reverse osmosis-treated PWWSs were observed to cluster with the untreated PWWSs, suggesting the need to adopt an advance and better wastewater treatment methods by the pharmaceutical industries.
... DCF is a very good visceral analgesic, being indicated in acute, moderate and severe pain in acute and chronic cholecystitis, renal colic pain, and in dysmenorrhea, as well as in postoperative and post-traumatic pain, neoplastic pain, inflammatory or degenerative arthritis (8,9,10,11,12). ...
... A modern and interesting direction of research is the design and study of ways to incorporate non-steroidal anti-inflammatory drugs (NSAIDs), agents frequently prescribed in medical practice for various diseases accompanied by pain, fever or inflammation (8,9). The phenylacetic acid derivative diclofenac is a NSAIDs with potent anti-inflammatory activity but also with a high risk of gastric irritation (9,22). ...
... The DCF-containing dressings (i.e., D2 and D4) also have a positive effect on cell viability. The improved cell viability of the DCF-containing (i.e., D2 and D4) samples compared to the drug-free (i.e., D1 and D3) samples is likely due to the anti-inflammatory properties of the DCF molecule [80,131,132]. Conversely, both samples with incorporated FePt NPs show a slightly negative effect on the cells. This could be due to the ability of the NPs, which were released into the cell growth medium after the dissolution of the polymer, to form reactive oxygen species (ROS). ...
This study presents an innovative wound dressing system that offers a highly effective therapeutic solution for treating painful wounds. By incorporating the widely used non-steroidal anti-inflammatory drug diclofenac, we have created an active wound dressing that can provide targeted pain relief with ease. The drug was embedded within a biocompatible matrix composed of polyhydroxyethyl methacrylate and polyhydroxypropyl methacrylate. The multilayer structure of the dressing, which allows for sustained drug release and an exact application, was achieved through the layer-by-layer coating technique and the inclusion of superparamagnetic iron platinum nanoparticles. The multilayered dressings’ physicochemical, structural, and morphological properties were characterised using various methods. The synergistic effect of the incorporated drug molecules and superparamagnetic nanoparticles on the surface roughness and release kinetics resulted in controlled drug release. In addition, the proposed multilayer wound dressings were found to be biocompatible with human skin fibroblasts. Our findings suggest that the developed wound dressing system can contribute to tailored therapeutic strategies for local pain relief.
