The double layer adsorption of sulfamethoxazole, ketoprofen and carbamazepine on a phosphorus carbon-based adsorbent was analyzed using statistical physics models. The objective of this research was to provide a physicochemical analysis of the adsorption mechanism of these organic compounds via the calculation of both steric and energetic parameters. Results showed that the adsorption mechanism of these pharmaceuticals was multimolecular where the presence of molecular aggregates (mainly dimers) could be expected in the aqueous solution. This adsorbent showed adsorption capacities at saturation from 15 to 36 mg/g for tested pharmaceutical molecules. The ketoprofen adsorption was exothermic, while the adsorption of sulfamethoxazole and carbamazepine was endothermic. The adsorption mechanism of these molecules involved physical interaction forces with interaction energies from 5.95 to 19.66 kJ/mol. These results contribute with insights on the adsorption mechanisms of pharmaceutical pollutants. The identification of molecular aggregates, the calculation of maximum adsorption capacities and the characterization of thermodynamic behavior provide crucial information for the understanding of these adsorption systems and to optimize their removal operating conditions. These findings have direct implications for wastewater treatment and environmental remediation associated with pharmaceutical pollution where advanced adsorption technologies are required.

Given that oxidative stress (OS) occurs as one of the complications of general anesthesia and surgical procedures, practicing the best and safest anesthesia regimen can have a significant share in various surgeries. So, this study compared the effects of non-steroidal anti-inflammatory drugs (NSAIDs) such as ketoprofen (KTP) and meloxicam (MLX) on OS through the glutathione pathway after the ketamine-xylazine (K-X) anesthesia and ulcer induction in rats to suggest post-operative regimens with promising analgesic and anti-inflammatory effects. 80 healthy adult male Wistar rats, were examined in this study. To obtain the baseline value cardiac blood collected of five rats, and the remaining 75 animals were randomized into three groups of 25, including (i) the control group receiving physiological serum, (ii) the experimental group 1 taking KTP, (iii) the experimental group 2, administered by MLX and all three groups received K-X combination IP after 30 min. Then, a full-thickness ulcer was induced under standard conditions, and the blood samples were collected from groups at T0, T30m, T60m, T24h, and T48h. The serum levels of the desired markers were measured. The study results revealed that the administration of K-X as an anesthetic agent made some changes in the markers of the OS-related glutathione (GSH) pathway. Moreover, KTP and MLX, significantly (p < 0.05) augmented the reduced GSH (rGSH), lowered the GSSG, increased the total values of the glutathione disulfide (GSSG) and the rGSH, reduced the rGSH/GSSG ratio, and accelerated the glutathione peroxidase (GPx) activity, but they had high inhibitory effects on the glutathione reductase (GR). Accordingly, both drugs could maintain the balance between the OS markers, caused by general anesthesia. In general, KTP can be a suitable regimen in surgeries wherein analgesia is of importance for less than 24 h, but MLX can be a preferable option if longer analgesia is needed for more than 24 h.

In the aquatic environment, the primary pollutants of heavy metals and pharmaceuticals always occur in coexisting forms, and the research about combined impacts remains unclear, especially transgenerational effects. Cadmium (Cd) is a heavy metal that can damage the endocrine reproduction systems and cause thyroid dysfunction in fish. Meanwhile, ketoprofen (KPF) is a nonsteroidal anti-inflammatory drug (NSAID) that can cause neurobehavioral damage and physiological impairment. However, to our knowledge, the combined exposure of Cd and KPF in transgenerational studies has not been reported. In this investigation, sexually mature zebrafish were subjected to isolated exposure and combined exposure to Cd (10 μg/L) and KPF (10 and 100 μg/L) at environmentally relevant concentrations for 42 days. In this background, breeding capacity, chemical accumulation rate in gonads, and tissue morphologies are investigated in parental fish. This is followed by examining the malformation rate, inflammation rate, and gene transcription in the F1 offspring. Our results indicate that combined exposure of Cd and KPF to the parental fish could increase the chemical accumulation rate and tissue damage in the gonads of fish and significantly reduce the breeding ability. Furthermore, these negative impacts were transmitted to its produced F1 embryos, reflected by hatching rate, body deformities, and thyroid axis-related gene transcription. These findings provide further insights into the harm posed by Cd in the presence of KPF to the aquatic ecosystems.

The emergence and spread of antibiotic resistance in the environment pose a serious threat to global public health. It is acknowledged that non-antibiotic stresses, including disinfectants, pharmaceuticals and organic pollutants, play a crucial role in horizontal transmission of antibiotic resistance genes (ARGs). Despite the widespread presence of non-steroidal anti-inflammatory drugs (NSAIDs), notably in surface water, their contributions to the transfer of ARGs have not been systematically explored. Furthermore, previous studies have primarily concentrated on model strains to investigate whether contaminants promote the conjugative transfer of ARGs, leaving the mechanisms of ARG transmission among antibiotic resistant bacteria in natural aqueous environments under the selective pressures of non-antibiotic contaminants remains unclear. In this study, the Escherichia coli (E. coli) K12 carrying RP4 plasmid was used as the donor strain, indigenous strain Aeromonas veronii containing rifampicin resistance genes in Taihu Lake, and E. coli HB101 were used as receptor strains to establish inter-genus and intra-genus conjugative transfer systems, examining the conjugative transfer frequency under the stress of ketoprofen. The results indicated that ketoprofen accelerated the environmental spread of ARGs through several mechanisms. Ketoprofen promoted cell-to-cell contact by increasing cell surface hydrophobicity and reducing cell surface charge, thereby mitigating cell-to-cell repulsion. Furthermore, ketoprofen induced increased levels of reactive oxygen species (ROS) production, activated the DNA damage-induced response (SOS), and enhanced cell membrane permeability, facilitating ARG transmission in intra-genus and inter-genus systems. The upregulation of outer membrane proteins, oxidative stress, SOS response, mating pair formation (Mpf) system, and DNA transfer and replication (Dtr) system related genes, as well as the inhibition of global regulatory genes, all contributed to higher transfer efficiency under ketoprofen treatment. These findings served as an early warning for a comprehensive assessment of the roles of NSAIDs in the spread of antibiotic resistance in natural aqueous environments.

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3 weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

Ketoprofen is a non-steroidal, anti-inflammatory drug frequently incorporated in topical dosage forms which are an interesting alternatives for oral formulations. However, due to the physiological barrier function of skin, topical formulations may require some approaches to improve drug permeation across the skin. In this study, ketoprofen-loaded microemulsion-based gels with the addition of menthol, commonly known for absorption-enhancing activity in dermal products, were investigated. The main objective of this study was to analyze the physicochemical properties of the obtained gels in terms of topical application and to investigate the correlation between the gel composition and its mechanical properties and the drug release process. Microemulsion composition was selected with the use of a pseudoternary plot and the selected systems were tested for electrical conductivity, viscosity, pH, and particle diameter. The polymer gels obtained with Carbopol® EZ-3 were subjected to rheological and textural studies, as well as the drug release experiment. The obtained results indicate that the presence of ketoprofen slightly decreased yield stress values. A stronger effect was exerted by menthol presence, even though it was independent of menthol concentration. A similar tendency was seen for hardness and adhesiveness, as tested in texture profile analysis. Sample cohesiveness and the drug release rate were independent of the gel composition.

The metastability of amorphous formulations poses barriers to their safe and widespread commercialization. The propensity of amorphous solid dispersions (ASDs) to crystallize is directly linked to their molecular structure. Amorphous structures are inherently complex and thus difficult to fully characterize by experiments, which makes structural simulations an attractive route for investigating which structural characteristics correlate with ASD stability. In this study, we use empirical potential structure refinement (EPSR) to create molecular models of ketoprofen-poly(vinylpyrrolidone) (KTP/PVP) ASDs with 0-75 wt % drug loading. The EPSR technique uses X-ray total scattering measurements as constraints, yielding models that are consistent with the X-ray data. We perform several simulations to assess the sensitivity of the EPSR approach to input parameters such as intramolecular bond rotations, PVP molecule length, and PVP tacticity. Even at low drug loading (25 wt %), ∼40% of KTP molecules participate in KTP-KTP hydrogen bonding. The extent of KTP-PVP hydrogen bonding does not decrease significantly at higher drug loadings. However, the models\' relative uncertainties are too large to conclude whether ASDs\' lower stabilities at high drug loadings are due to changes in drug-excipient hydrogen bonding or a decrease in steric hindrance of KTP molecules. This study illustrates how EPSR, combined with total scattering measurements, can be a powerful tool for investigating structural characteristics in amorphous formulations and developing ASDs with improved stability.

Ketoprofen (KET), as a non-steroidal anti-inflammatory drug frequently detected in aqueous environments, is a threat to human health due to its accumulation and low biodegradability, which requires the transformation and degradation of KET in aqueous environments. In this paper, the reaction process of ozone-initiated KET degradation in water was investigated using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The detailed reaction path of KET ozonation is proposed. The thermodynamic results show that ozone-initiated KET degradation is feasible. Under ultraviolet irradiation, the reaction of ozone with water can also produce OH radicals (HO·) that can react with KET. The degradation reaction of KET caused by HO· was further studied. The kinetic calculation illustrates that the reaction rate (1.99 × 10-1 (mol/L)-1 sec-1) of KET ozonation is relatively slow, but the reaction rate of HO· reaction is relatively high, which can further improve the degradation efficiency. On this basis, the effects of pollutant concentration, ozone concentration, natural organic matter, and pH value on degradation efficiency under UV/O3 process were analyzed. The ozonolysis reaction of KET is not sensitive to pH and is basically unaffected. Finally, the toxicity prediction of oxidation compounds produced by degradation reaction indicates that most of the degradation products are harmless, and a few products containing benzene rings are still toxic and have to be concerned. This study serves as a theoretical basis for analyzing the migration and transformation process of anti-inflammatory compounds in the water environment.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

OBJECTIVE: To evaluate and compare the effect of dexamethasone, ketoprofen and cold compress on the quality of life (QoL) following surgical removal of impacted lower third molars (ILTMs).
METHODS: Eligible patients requiring ILTM extraction with a modified Pederson difficulty index score of 5-6 were recruited. The patients were randomly allocated into Groups A, B and C. Groups A and C received 100 mg of ketoprofen and 8 mg of dexamethasone per-oral respectively, preoperatively. Subjects in group B applied a pre-standardized ice pack over the angle of the mandible for 6 h postoperatively. The QoL questionnaire was administered on postoperative days 1, 2 and 7.
RESULTS: In total, seventy-eight subjects completed the study: 46 (59%) were male and had a mean age of 27.8 ± 4.9 years. The groups were similar sociodemographically. The overall QoL and appearance domain score were significantly better in patients on oral dexamethasone on postoperative day 1 than in the other groups.
CONCLUSIONS: Oral dexamethasone demonstrates better improvement in postoperative QoL and appearance on day 1 following ILTM surgery compared to ice packs and ketoprofen. Although ice packs are readily available, can be used repeatedly and are a low-cost option, more research is necessary to determine their optimum therapeutic use in outpatient settings.
CONCLUSIONS: Oral dexamethasone is superior to ice pack compress and ketoprofen in improving the postoperative QoL in ILTM surgery.
UNASSIGNED: PACTR202005593102009 at Pan African Clinical Trial Registry.