Search Results (805)

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Background: Inflammation abrogates cellular organization and tissue homoeostasis, resulting in redness, swelling, heat, pain, and loss of function. A model of carrageenan-induced paw edema (CIE) is commonly utilized to test anti-inflammatory substances. Based on the ability of Lepisanthes alata (LA), a tropical plant that is rich in phytochemicals like polyphenols, this study assessed the optimal dose and the health benefits of LA in rats that had been induced with carrageenan to develop paw swelling. Methods: Twenty-four male Wistar rats were divided into four groups to which carrageenan was administered, after which, distilled water at oral dose (C + DW), sodium diclofenac 25 mg/kg (C + DS), LA extract in 250 mg/kg (C + LA250), and 500 mg/kg (C + LA500) was given, respectively. Paw edema was assessed in 24 h. Pain was assessed using the Rat Grimace Scale (RGS), cytokines, antioxidant activity, and tissue changes. Results: LA at 250 and 500 mg/kg significantly decreased paw edema and inflammatory markers in the results of both studies. Remarkably, LA 250 mg/kg significantly decreased RGS scores as well as IL-1β, TNF-α, and histological inflammation but had a positive effect on T-SOD levels. Conclusions: LA extract, especially at 250 mg/kg, shows potent anti-inflammatory, analgesic, and antioxidant properties in CIE rats. Full article

Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article

In response to the European Union’s revised Urban Wastewater Treatment Directive, which mandates enhanced monitoring and advanced treatment of micropollutants, this study was conducted. It took place within the Coastal Landscape Park (CLP), a Natura 2000 protected area in northern Poland. The focus was on the municipal wastewater treatment plant in Jastrzębia Góra, located in a region exposed to seasonal tourist pressure and discharging effluent into the Czarna Wda River. A total of 90 wastewater samples were collected during five monitoring campaigns (July, September 2021; February, May, July 2022) and analysed for 13 pharmaceuticals and personal care products (PPCPs) using ultra-high-performance liquid chromatography tandem mass spectrometry with electrospray ionisation (UHPLC-ESI-MS/MS). The monitoring included both untreated (UTWW) and treated wastewater (TWW) to assess the PPCP removal efficiency and persistence. The highest concentrations in the treated wastewater were observed for metoprolol (up to 472.9 ng/L), diclofenac (up to 3030 ng/L), trimethoprim (up to 603.6 ng/L) and carbamazepine (up to 2221 ng/L). A risk quotient (RQ) analysis identified diclofenac and LI-CBZ as priority substances for monitoring. Multivariate analyses (PCA, HCA) revealed co-occurrence patterns and seasonal trends. The results underline the need for advanced treatment solutions and targeted monitoring, especially in sensitive coastal catchments with variable micropollutant presence. Full article

Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during the pandemic of coronavirus disease 2019 as well as diclofenac and ibuprofen. However, the detailed mode of analgesic action of acetaminophen is still unclear. In the present study, we comprehensively discuss conventional, recognized, and postulated mechanisms of analgesic acetaminophen and highlight the current mechanistic concepts while comparing with diclofenac and ibuprofen. Acetaminophen inhibits cyclooxygenase with selectivity for cyclooxygenase-2, which is higher than that of ibuprofen but lower than that of diclofenac. In contrast to diclofenac and ibuprofen, however, anti-inflammatory effects of acetaminophen depend on the extracellular conditions of inflamed tissues. Since the discovery of cyclooxygenase-3 in the canine brain, acetaminophen had been hypothesized to inhibit such a cyclooxygenase-1 variant selectively. However, this hypothesis was abandoned because cyclooxygenase-3 was revealed not to be physiologically and clinically relevant to humans. Recent studies suggest that acetaminophen is deacetylated to 4-aminophenol in the liver and after crossing the blood–brain barrier, it is metabolically converted into N-(4-hydroxyphenyl)arachidonoylamide. This metabolite exhibits bioactivities by targeting transient receptor potential vanilloid 1 channel, cannabinoid receptor 1, Cav3.2 calcium channel, anandamide, and cyclooxygenase, mediating acetaminophen analgesia. These targets may be partly associated with diclofenac and ibuprofen. The perspective of acetaminophen as a prodrug will be crucial for a future strategy to develop analgesics with higher tolerability and activity. Full article

This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion. Full article

Highly porous organosilicas were synthesized via direct co-condensation of two monomers, bis (triethoxysilyl) benzene and aminopropyltriethoxysilane, by adjusting the time between consecutive additions of the monomers and the ageing time of the as-obtained samples. The resulting organosilicas exhibited high porosities, with total pore volumes exceeding 2.2 cm³/g. Alongside detailed insights into the morphology, structure, and surface chemistry via a broad spectrum of various instrumental techniques, the obtained ultraporous amine-functionalized organosilicas were tested as adsorbents of diclofenac sodium, chosen here as a model drug. The results revealed remarkable differences in the physicochemical properties and adsorption efficiencies among the obtained samples, confirming that the time gap between the addition of the monomers and ageing time can be used to tune the morphological, structural, and chemical features of the obtained organosilicas and, as a consequence, their sorption efficiencies. Full article

Background/Objectives: Hepatic clearance is important in determining clinical drug administration strategies. Achieving accurate hepatic clearance predictions through in vitro-to-in vivo extrapolation (IVIVE) relies on appropriate model selection, which is a critical step. Although numerous models have been developed to estimate drug dosage, some may fail to predict liver drug clearance owing to inappropriate hepatic clearance models during IVIVE. To address this limitation, an in silico-based model selection approach for optimizing hepatic clearance predictions was introduced in a previous study. The current study extends this strategy by verifying the accuracy of the selected models using ex situ experimental data, particularly for drugs whose model choices are influenced by protein binding. Methods: Commonly prescribed drugs were classified according to their hepatic extraction ratios and protein-binding properties. Building on previous studies that employed multinomial logistic regression analysis for model selection, a three-phase classification method was implemented to identify five representative drugs: diazepam, diclofenac, rosuvastatin, fluoxetine, and tolbutamide. Subsequently, an isolated perfused rat liver (IPRL) system was used to evaluate the accuracy of the in silico method. Results: As the unbound fraction increased for diazepam and diclofenac, the most suitable predictive model shifted from the initially preferred well-stirred model (WSM) to the modified well-stirred model (MWSM). For rosuvastatin, the MWSM provided a more accurate prediction. These three capacity-limited, binding-sensitive drugs conformed to the outcomes predicted by the multinomial logistic regression analysis. Fluoxetine was best described by the WSM, which is consistent with its flow-limited classification. For tolbutamide, a representative capacity-limited, binding-insensitive drug, no significant differences were observed among the various models. Conclusions: These findings demonstrate the accuracy of an in silico-based model selection approach for predicting liver metabolism and highlight its potential for guiding dosage adjustments. Furthermore, the IPRL system serves as a practical tool for validating the accuracy of the results derived from this approach. Full article

Pharmaceuticals such as diclofenac (DCF), a widely used anti-inflammatory drug, are frequently detected in water bodies and pose serious environmental and health risks due to their persistence and low biodegradability. Although ozonation is an effective method for pollutant removal, its efficiency is often limited by low ozone utilization and incomplete mineralization. In this work, CuO/Al₂O₃- and MnO₂/Al₂O₃-supported catalysts were prepared via an impregnation method and evaluated for their performance in catalytic ozonation of diclofenac (DCF) in an aqueous solution. The catalysts were characterized by TEM, N₂ adsorption–desorption, FTIR, and XPS analyses. The effects of catalyst type, dosage, initial pH, and ozone flow rate on degradation efficiency were systematically investigated. Under optimal conditions, the DCF removal efficiencies reached 73.99% and 76.33% using CuO/Al₂O₃ and MnO₂/Al₂O₃, respectively, while COD removal efficiencies were 77.6% and 89.3%. Quenching experiments indicated that hydroxyl radicals (•OH) were the predominant reactive species involved in the catalytic ozonation process. The results demonstrate that supported CuO and MnO₂ catalysts can effectively enhance diclofenac degradation by ozone, offering potential for advanced water treatment applications. Full article

Removal of micropollutants using biological treatment systems remains a challenge, since conventional bioprocess systems require adaptations to provide more advanced treatment. An ambient temperature upflow anaerobic sludge blanket (UASB) reactor was employed, followed by a two-stage (saturated and unsaturated) vertical subsurface flow (VSSF) constructed wetland (CW) system, to treat domestic wastewater from a nearby settlement and investigate the occurrence and fate of 10 contaminants of emerging concern (CECs) in decentralized, non-conventional treatment systems. The integrated UASB—two-stage CW system achieved high performance regarding abatement of target CECs across all periods. Removal efficiencies ranged from 78% ± 21% (ketoprofen) to practically 100% (2-hydroxybenzothiazole). The pilot system was found to be robust performance-wise and provided enhanced treatment in comparison to a conventional wastewater treatment plant operating in parallel. Most of the target CECs were successfully treated by UASB, saturated and unsaturated CWs, while ibuprofen, bisphenol A and diclofenac were mostly removed in the unsaturated CW. Environmental risk assessment revealed that triclosan poses a significant ecological risk to algae during treated wastewater disposal into the aquatic environment. Additionally, cumulative risk quotient indicated that the potential for mixture toxicity should be carefully considered across all trophic levels. Full article

Diclofenac is an effective medication for pain and inflammation. However, its use has been linked to hepatitis. To gain insight into diclofenac’s ability to cause hepatitis, we investigated the regulation of major effectors of the immune system following daily treatment of minipigs at 3 and 15 mg/kg for 28 days. Histopathology evidenced lobular inflammation, and through a combination of immunogenomics and immunopathology, we detected marked innate and adaptive immune responses. We identified 109 significantly regulated genes linked to neutrophil, monocyte, Kupffer cell, and lymphocyte responses and 32 code for cytokine- and interferon-γ-signaling. In support of wound repair, immunopathology evidenced manifest upregulation of macrophage migration inhibitory factor and CD74. Furthermore, the strong expression of IgG and IgM underscored humoral immune responses. Diclofenac caused an activation of the complement system, especially the C1 inhibitor of the classical pathway and C3 with critical functions in liver regeneration. The marked expression of complement factor B and H of the alternate pathway modulated B-cell responses. Likely, the upregulation of factor H protected hepatocytes from injury by limiting complement-mediated damage of inflamed cells. Additionally, diclofenac treatment elicited marked hepatic expression of lysozyme and KLF6. The latter earmarks M1-polarized Kupffer cells. We observed an extraordinary induction of calprotectin/S100A9 and of the monocyte/macrophage CD163 scavenger receptor, and therefore, we detected innate immune sensing of damaged cells. Lastly, we noted an unprecedented induction of the acute phase reactant SAA1 and DEC-205, which recognize apoptotic and necrotic cells. Together, our results offer mechanistic insights into immune-mediated liver injury patterns following diclofenac treatment. Full article

The work aimed to investigate the presence of pharmaceutical compounds from the anti-inflammatory class in seawater from the Romanian Black Sea coast and to assess the ecological risk of these substances on the most sensitive organisms. Using the solid-phase extraction technique (SPE) followed by liquid chromatography separation and mass spectrometry detection (LC-MS/MS) of the compounds, the concentrations of these contaminants in selected seawater samples were determined. Ibuprofen was the most commonly detected compound with a frequency of 42.9%, followed by ketoprofen at 31.0.%, diclofenac at 23.8%, and naproxen at 21.4%. The maximum concentrations of pharmaceutical products varied between 13.4 ng/L ketoprofen and 13,575 ng/L caffeine. The order of decreasing maximum concentrations of pharmaceutical compounds in the water of the Black Sea was CAF > IBU > NAP > DIC > KET. The dominant and ubiquitous compound that was determined with the maximum concentration values was caffeine. Strong correlations were observed between three compounds (naproxen: diclofenac, diclofenac: ketoprofen) suggesting the same pollution source. Through the ecological risk assessment, it was observed that both caffeine and ibuprofen can generate high ecological risks for some echinoderms, crustaceans, and fish. Full article

Research on using biochar as an adsorbent of contaminants in aqueous matrices has gained significant relevance in recent years due to the surface chemistry and porous structure of biochar, which facilitate the retention of a wide range of pollutants. This study explores the adsorption performance of a novel biochar produced from agave bagasse—a readily available agro-industrial waste in Mexico—through low-temperature pyrolysis. The biochar was evaluated for its capacity to remove conventional water quality parameters (chemical oxygen demand (COD), nitrates (NO₃⁻), total nitrogen (TN), total phosphorus (TP), ammonium (NH₄⁺), turbidity, apparent color, and true color) from water samples collected from the polluted Bustillos Lagoon in Chihuahua, Mexico. Additionally, the removal of emerging pharmaceutical contaminants, specifically acetaminophen (Act) and diclofenac (Dfc), was assessed in synthetic aqueous solutions. Potentiometric titration analyses revealed a significant contribution of surface acidity in the adsorption of pharmaceutical derivatives, highlighting the relevance of functional groups retained during low-temperature pyrolysis. The biochar derived from agave bagasse (BBAF1) was tested in a fixed-bed column system and compared with two commercial activated carbons (CACCF2 and CVCF3). The BBAF1 biochar achieved average removal efficiencies ranging from 50% to 90% for all conventional parameters. In contrast, those of ACT and DFC were between 0.43 and 0.67 mg g⁻¹ (59–85%) and 0.34 and 0.62 mg g⁻¹ (37–79%), respectively, demonstrating their potential as an adsorbent material for improving water quality. This work supports the development of circular economic strategies by valorizing agricultural residues while offering an effective solution to environmental pollution challenges. Full article

Nanotechnology has emerged as a highly focused field of research due to the unique properties of nanometric materials, particularly their large specific surface areas and excellent adsorption capabilities. This study investigated the synthesis of materials based on graphene oxide (GO) functionalized with different metal oxides (MnO₂, Fe₃O₄, CuO, NiO), with potential applications in water decontamination. The morphological, structural, and compositional properties of these nanocomposites were extensively characterized using different experimental techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and vibrating sample magnetometry (VSM) for magnetic property evaluation. Preliminary adsorption tests were performed for the removal of pesticides and drugs from aqueous solutions. The synthesized materials demonstrated a higher affinity for selected pesticides compared to drugs. The best removal efficiencies were 98.59% for cymoxanil, 97.93% for triadimefon, 63.33% for sulfamethoxazole, and 99.59% for diclofenac. The results indicate that the functionalization of GO with metal oxides modifies the material’s structure, increasing its potential for environmental applications such as water purification. Full article

The removal of pharmaceutical contaminants like the anticonvulsant carbamazepine (CBZ) from water sources is a growing environmental challenge. This study explores the development of molecularly imprinted polymers (MIPs) tailored for CBZ adsorption using a bulk polymerization approach. Initially, this study focused on selecting the optimal cross-linker, comparing a trifunctional (trimethylolpropane triacrylate, TRIM) and a bifunctional cross-linker (ethylene glycol dimethacrylate, EGDMA) in combination with two common monomers (2-vinylpyridine and methacrylic acid). TRIM-based MIPs demonstrated superior adsorption efficiency and stability due to their higher cross-linking density. To improve sustainability, six bio-based monomers were investigated; of these, eugenol (EUG) and coumaric acid (COU) showed the best CBZ affinity due to π-π interactions and hydrogen bonding. Adsorption tests conducted in pharmaceutical-spiked real wastewater demonstrated that MIPs exhibit a high selectivity for CBZ over other pharmaceuticals like the anti-inflammatory drugs diclofenac (DCF) and ibuprofen (IBU), even at high concentrations. Reaction conditions were further optimized by adjusting the reaction time and the ratio between reagents to enhance selectivity and adsorption performance. These results highlight the potential of bio-based MIPs as efficient and selective materials for the removal of pharmaceutical pollutants from wastewater. Full article