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1.
J Environ Sci (China) ; 147: 451-461, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003061

ABSTRACT

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.


Subject(s)
Ketoprofen , Ozone , Water Pollutants, Chemical , Ketoprofen/chemistry , Ozone/chemistry , Water Pollutants, Chemical/chemistry , Kinetics , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Models, Chemical , Water Purification/methods
2.
Gels ; 10(7)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-39057458

ABSTRACT

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.

3.
Mol Pharm ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018110

ABSTRACT

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.

4.
Drug Chem Toxicol ; : 1-16, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38910278

ABSTRACT

The growing concern about pollution and toxicity in aquatic as well as terrestrial organisms is predominantly caused due to waterborne exposure and poses a risk to environmental systems and human health. This study addresses the co-toxic effects of cadmium (Cd) and ketoprofen (KPF), representing heavy metal and pharmaceutical discharge pollutants, respectively, in aquatic ecosystems. A 96-h acute toxicity assessment was conducted using zebrafish embryos. The results indicated that high dosages of KPF (10, 15, and 100 µg/mL) and Cd (10 and 15 µg/mL) reduced survivability and caused concentration-dependent deformities such as scoliosis and yolk sac edema. These findings highlight the potential defects in development and metabolism, as evidenced by hemolysis tests demonstrating dose-dependent effects on blood cell integrity. Furthermore, this study employs adult zebrafish for a 42-day chronic exposure to Cd and KPF (10 and 100 µg/L) alone or combined (10 + 10 and 100 + 100 µg/L) to assess organ-specific Cd and KPF accumulation in tissue samples. Organ-specific accumulation patterns underscore complex interactions impacting respiratory, metabolic, and detoxification functions. Prolonged exposure induces reactive oxygen species formation, compromising antioxidant defense systems. Histological examinations reveal structural changes in gills, gastrointestinal, kidney, and liver tissues, suggesting impairments in respiratory, osmoregulatory, nutritional, and immune functions. This study emphasizes the importance of conducting extensive research on co-toxic effects to assist with environmental risk assessments and safeguard human health and aquatic ecosystems.

5.
Oral Maxillofac Surg ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38926204

ABSTRACT

OBJECTIVES: 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). MATERIALS AND 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. CLINICAL RELEVANCE: Oral dexamethasone is superior to ice pack compress and ketoprofen in improving the postoperative QoL in ILTM surgery. TRIAL REGISTRY REGISTRATION NUMBER: PACTR202005593102009 at Pan African Clinical Trial Registry.

6.
ACS Biomater Sci Eng ; 10(6): 3833-3841, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38747490

ABSTRACT

This study explores the realm of personalized medicine by investigating the utilization of 3D-printed dosage forms, specifically focusing on patient-specific enteric capsules designed for the modified release of ketoprofen, serving as a model drug. The research investigates two distinct scenarios: the modification of drug release from 3D-printed capsules crafted from hydroxypropyl methylcellulose phthalate:polyethylene glycol (HPMCP:PEG) and poly(vinyl alcohol) (PVA), tailored for pH sensitivity and delayed release modes, respectively. Additionally, a novel ketoprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) based on pomegranate seed oil (PSO) was developed, characterized, and employed as a fill material for the capsules. Through the preparation and characterization of the HPMCP:PEG based filament via the hot-melt extrusion method, the study thoroughly investigated its thermal and mechanical properties. Notably, the in vitro drug release analysis unveiled the intricate interplay between ketoprofen release, polymer type, and capsule thickness. Furthermore, the incorporation of ketoprofen into the SNEDDS exhibited an enhancement in its in vitro cylooxygenase-2 (COX-2) inhibitory activity. These findings collectively underscore the potential of 3D printing in shaping tailored drug delivery systems, thereby contributing significantly to the advancement of personalized medicine.


Subject(s)
Capsules , Drug Liberation , Emulsions , Ketoprofen , Precision Medicine , Printing, Three-Dimensional , Ketoprofen/chemistry , Precision Medicine/methods , Humans , Emulsions/chemistry , Polyethylene Glycols/chemistry , Drug Delivery Systems/methods , Delayed-Action Preparations , Methylcellulose/chemistry , Methylcellulose/analogs & derivatives , Polyvinyl Alcohol/chemistry
7.
Pharmaceuticals (Basel) ; 17(5)2024 May 14.
Article in English | MEDLINE | ID: mdl-38794197

ABSTRACT

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.

8.
Molecules ; 29(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38792157

ABSTRACT

Deep eutectic solvents (DESs) are commonly used in pharmaceutical applications as excellent solubilizers of active substances. This study investigated the tuning of ibuprofen and ketoprofen solubility utilizing DESs containing choline chloride or betaine as hydrogen bond acceptors and various polyols (ethylene glycol, diethylene glycol, triethylene glycol, glycerol, 1,2-propanediol, 1,3-butanediol) as hydrogen bond donors. Experimental solubility data were collected for all DES systems. A machine learning model was developed using COSMO-RS molecular descriptors to predict solubility. All studied DESs exhibited a cosolvency effect, increasing drug solubility at modest concentrations of water. The model accurately predicted solubility for ibuprofen, ketoprofen, and related analogs (flurbiprofen, felbinac, phenylacetic acid, diphenylacetic acid). A machine learning approach utilizing COSMO-RS descriptors enables the rational design and solubility prediction of DES formulations for improved pharmaceutical applications.


Subject(s)
Deep Eutectic Solvents , Ibuprofen , Ketoprofen , Machine Learning , Solubility , Ketoprofen/chemistry , Ibuprofen/chemistry , Deep Eutectic Solvents/chemistry , Cyclooxygenase Inhibitors/chemistry , Hydrogen Bonding , Solvents/chemistry
9.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473945

ABSTRACT

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of the potential impurities of dexketoprofen, including the distomer R-ketoprofen. After screening the separation capability of four polysaccharide columns (Lux Amylose-1, Lux Amylose-2, Lux Cellulose-1 and Lux Cellulose-2) in polar organic and in reversed-phase modes, appropriate enantioseparation was observed only on the Lux Amylose-2 column in an acidified acetonitrile/water mixture. A detailed investigation of the mobile phase composition and temperature for enantio- and chemoselectivity showed many unexpected observations. It was observed that both the resolution and the enantiomer elution order can be fine-tuned by varying the temperature and mobile phase composition. Moreover, hysteresis of the retention times and enantioselectivity was also observed in reversed-phase mode using methanol/water mixtures on amylose-type columns. This could indicate that the three-dimensional structure of the amylose column can change by transitioning from a polar organic to a reversed-phase mode, which affects the enantioseparation process. Temperature-dependent enantiomer elution order and rare enthalpic/entropic controlled enantioseparation in the operative temperature range were also observed in reversed-phase mode. To find the best methodological conditions for the determination of dexketoprofen impurities, a full factorial optimization design was performed. Using the optimized parameters (Lux Amylose-2 column with water/acetonitrile/acetic acid 50/50/0.1 (v/v/v) at a 1 mL/min flow rate at 20 °C), baseline separations were achieved between all compounds within 15 min. Our newly developed HPLC method was validated according to the current guidelines, and its application was tested on commercially available pharmaceutical formulations. According to the authors' knowledge, this is the first study to report hysteretic behavior on polysaccharide columns in reversed-phase mode.


Subject(s)
Amylose , Chromatography, Reverse-Phase , Ketoprofen/analogs & derivatives , Tromethamine , Amylose/chemistry , Temperature , Polysaccharides/chemistry , Cellulose/chemistry , Chromatography, High Pressure Liquid/methods , Water , Acetonitriles , Stereoisomerism
10.
Bioengineering (Basel) ; 11(3)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38534533

ABSTRACT

Despite rapid progress in tissue engineering, the repair and regeneration of bone defects remains challenging, especially for non-homogenous and complicated defects. We have developed and characterized biodegradable drug-eluting scaffolds for bone regeneration utilizing direct powder extrusion-based three-dimensional (3D) printing techniques. The PLGA scaffolds were fabricated using poly (lactic-co-glycolic acid) (PLGA) with inherent viscosities of 0.2 dl/g and 0.4 dl/g and ketoprofen. The effect of parameters such as the infill, geometry, and wall thickness of the drug carrier on the release kinetics of ketoprofen was studied. The release studies revealed that infill density significantly impacts the release performance, where 10% infill showed faster and almost complete release of the drug, whereas 50% infill demonstrated a sustained release. The Korsmeyer-Peppas model showed the best fit for release data irrespective of the PLGA molecular weight and infill density. It was demonstrated that printing parameters such as infill density, scaffold wall thickness, and geometry played an important role in controlling the release and, therefore, in designing customized drug-eluting scaffolds for bone regeneration.

11.
Mikrochim Acta ; 191(4): 218, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530416

ABSTRACT

An electrochemical sensor for detecting ketoprofen was constructed by in-situ grown copper cobaltate (CuCo2O4) nanoneedle arrays on a carbon cloth (CC) substrate. The resulting porous nanoneedle arrays not only expose numerous electrochemically active sites but also significantly enhance the electrochemical apparent active area and current transmission efficiency. By leveraging its electrochemical properties, the sensor achieves an impressive detection limit for ketoprofen of 0.7 pM, with a linear range spanning from 2 pM ~ 2 µM. Furthermore, the sensor exhibits remarkable reproducibility, anti-interference capabilities, and stability. Notably, the developed sensor also performed ketoprofen detection on real samples (including drug formulations and wastewater) and demonstrated excellent recognition ability. These exceptional performances can be attributed to the direct growth of CuCo2O4 nanoneedle arrays on the CC substrate, which facilitates a robust electrical connection, provides abundant electrocatalytic active sites, and expands the apparent active area. Consequently, these improvements contribute to the efficient trace detection capabilities of the ketoprofen sensor.

12.
Chemistry ; 30(23): e202303530, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38517291

ABSTRACT

Among inherently chiral selectors of axial stereogenicity, usually resulting in very good enantiodiscrimination performances, the biindole-based family has the additional advantage of very easy functionalization of the two nitrogen atoms with a variety of substituents with desirable properties. Aiming to evaluate the possibility of exploiting such feature to enhance the enantiodiscrimination ability of the archetype structure, a series of three inherently chiral monomers were designed and synthesized, characterised by a 2,2'-biindole atropisomeric core conjugated to bithiophene wings enabling fast and regular electrooligomerization, and functionalised at the nitrogen atoms with an ethyl, a methoxyethyl, or a hydroxyethyl substituent. Nitrogen alkylation was also exploited to obtain for the first time the chemical resolution of the biindole selectors without employing chiral HPLC. The enantiodiscrimination ability of the selector series was comparatively evaluated in proof-of-concept chiral voltammetry experiments with a "benchmark" chiral ferrocenyl probe as well as with chiral non-steroidal anti-inflammatory drugs naproxen and ketoprofen. The large enantiomer potential differences for all probes increased in the ethyl < methoxyethyl ≪ hydroxyethyl sequence of selector substituents, supporting our assumption on the beneficial role of an additional coordination element. The powerful hydroxyethyl selector was also applied to ketoprofen in a commercial drug matrix.

13.
Sci Rep ; 14(1): 4398, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38388671

ABSTRACT

In the current work, luffa was modified with silver nanoparticles to prepare LF/AgNPs adsorbent for the elimination of ketoprofen and reactive yellow 15 (RY15) from aqueous media. Various characterization techniques, including FT-IR, XRD, BET, and SEM-EDS analysis, were employed to confirm the successful modification of LF/AgNPs. Several key parameters such as contact time, adsorbent dosage, concentration, pH, and agitation technique were fine-tuned to optimize the adsorption process. Ketoprofen removal was found to be most effective in weakly acidic conditions (pH = 5), while reactive yellow 15 adsorption was enhanced in an acidic environment (pH = 2). At 298 K, the highest adsorption capacities reached 56.88 mg/g for ketoprofen and 97.76 mg/g for reactive yellow 15. In both scenarios involving the elimination of ketoprofen and RY15, the Temkin isotherm exhibits higher R2 values, specifically 0.997 for ketoprofen and 0.963 for RY15, demonstrating a strong correlation with the observed adsorption data. Additionally, the kinetics of ketoprofen adsorption were best described by the Pseudo-first order model (R2 = 0.989), whereas the Pseudo-second order model provided the most accurate fit for reactive yellow 15 adsorption (R2 = 0.997). Importantly, the LF/AgNPs adsorbent displayed consistent performance over five consecutive reuse cycles, affirming its stability and efficacy in removing both contaminants. These findings underscore the exceptional potential of LF/AgNPs as a reliable adsorbent for the removal of reactive yellow 15 and ketoprofen from aqueous solutions.

14.
J Conserv Dent Endod ; 27(1): 24-28, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38389736

ABSTRACT

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as a postoperative medication after endodontic treatment. The introduction of transdermal patches aided in reducing the discomfort caused by medication prescribed through the oral route. Aim: This study aims to compare the efficacy of transdermal patches of diclofenac and ketoprofen for postendodontic pain control. Materials and Methods: Thirty patients with symptomatic irreversible pulpitis in singlerooted teeth of either arch were endodontically treated by a single endodontist. Oral diclofenac for Group I and transdermal diclofenac patch for Group II and transdermal ketoprofen patch for Group III were administered as postendodontic analgesics. Visual Analog Scale chart was used to record pain intensity preoperatively and at intervals of 4, 8, and 24 h postoperatively. Paracetamol 500 mg tablets were provided as rescue medication. Statistical Analysis: Repeated Measure ANOVA. Results: There was a significant decrease in the postoperative pain intensity scores for both transdermal groups. The postoperative scores gradually decreased from day 1 to day 2. Six out of ten patients who had received diclofenac tablets complained of gastric discomfort. Conclusion: Both transdermal ketoprofen and diclofenac patches were effective than oral diclofenac tablet and can be used as an alternative and effective analgesic for postendodontic pain management, especially in patients with gastric discomfort.

15.
Chempluschem ; 89(5): e202300734, 2024 May.
Article in English | MEDLINE | ID: mdl-38216541

ABSTRACT

Four alkaline earth metal complexes of ketoprofen (Hket) and indomethacin (Hind) were synthesized and characterized: [Ca(ket)2(H2O)2]n (1), [Mg(ket)2(H2O)2] (2), [Ca(ind)2(EtOH)2]n (3), and [Mg(ind)2(EtOH)2] (4). All compounds were studied by elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Crystal structures of 1 and 3 were determined by single crystal X-ray diffraction technique T=100 K. The structure of 1 is dominated by a one-dimensional coordination polymer, while 3 is formed by a two-dimensional layer stabilized by the calcium zig-zag chains and π⋅⋅⋅π stacking interactions. Crystal packing arrangements were characterized by fingerprint plots (FPs) that were derived from the Hirshfeld surfaces (HSs). The antioxidant and antimicrobial activities of complexes were evaluated against Gram-positive and Gram-negative bacteria as well as yeasts.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Antioxidants , Coordination Complexes , Microbial Sensitivity Tests , Polymers , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Crystallography, X-Ray , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Polymers/chemistry , Polymers/chemical synthesis , Polymers/pharmacology , Calcium/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Models, Molecular , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Indomethacin/pharmacology , Indomethacin/chemistry
16.
Odontology ; 112(3): 826-838, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38265514

ABSTRACT

This study explored the antimicrobial effects of ketoprofen, piroxicam, and celecoxib alone or combined with calcium hydroxide (CH) against two strains of Enterococcus faecalis (E. faecalis) and assessed the influence of such combinations on the pH of CH. Minimum inhibitory concentrations (MICs) of the three tested NSAIDs were determined. Tested pastes were placed into wells punched in seeded agar plates and the bacterial inhibition zones were measured. Antibiofilm activity was assessed against 3 weeks of biofilm induced in bovine dentine blocks. The pH of the pastes was measured at four-time intervals. MIC values were 3.12, 25, and 25 mg/ml for ketoprofen, piroxicam, and celecoxib, respectively, and were similar for both bacterial strains except for celecoxib, which showed 8% growth at the highest tested concentration against vancomycin-resistant E. faecalis. Ketoprofen had the largest mean inhibition zone that was comparable to CH. None of the six tested pastes exhibited antibiofilm activity of a significant level in comparison to CH. A noticeable increase in the antibiofilm activity was found when 20% NSAIDs were added to CH while maintaining an alkaline pH. Ketoprofen was found to be the most effective among the tested NSAIDs. Although its effect was comparable to CH, adding ketoprofen at a ratio of 20% resulted in 50% higher antimicrobial action than CH alone. Accordingly, incorporating NSAIDs in inter-appointment dressing has the potential to utilize their anti-inflammatory, local analgesic, and antibacterial actions, which overcome the limitations of CH and improve the outcome of root canal treatment.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Biofilms , Calcium Hydroxide , Enterococcus faecalis , Microbial Sensitivity Tests , Calcium Hydroxide/pharmacology , Enterococcus faecalis/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Animals , Cattle , Biofilms/drug effects , In Vitro Techniques , Piroxicam/pharmacology , Ketoprofen/pharmacology , Celecoxib/pharmacology , Hydrogen-Ion Concentration , Root Canal Irrigants/pharmacology
17.
Environ Pollut ; 345: 123458, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38290656

ABSTRACT

Indirect photolysis induced by naturally occurring sensitizers constitutes an important pathway accounting for the transformation and fate of many recalcitrant micropollutants in sunlit surface waters. However, the photochemical transformation of micropollutants by photosensitizing pharmaceuticals has been less investigated. In this study, we demonstrated that the non-steroidal anti-inflammatory drug ketoprofen (KTF) and its photoproducts, 3-acetylbenzophenone (AcBP) and 3-ethylbenzophenone (EtBP), could sensitize the photodegradation of coexisting sulfonamide antibiotics, e.g., sulfamethoxazole (SMX), under artificial 365 nm ultraviolet (UV) and sunlight irradiation. Key reactive species including triplet excited state and singlet oxygen (1O2) responsible for photosensitization were identified by laser flash photolysis (LFP) and electron paramagnetic resonance (EPR) techniques, respectively. High-resolution mass spectrometry (HRMS) and structure-related reactivity analyses revealed that the sensitized photolysis of SMX occurred mainly through single electron transfer. The rate constants of sulfonamides sensitized by AcBP photolysis followed the order of sulfisoxazole (SIX)>sulfathiazole (STZ)>SMX>sulfamethizole (SMT). Exposure to sunlight also enhanced the photolysis of SMX in the presence of KTF or AcBP, and water matrix had limited impact on such process. Overall, our results reveal the feasibility and mechanistic aspects of photosensitization of coexisting contaminants by pharmaceuticals (or their photoproducts) and provide new insights into the cocktail effects of pharmaceutical mixtures on their photochemical behaviors in aqueous environment.


Subject(s)
Ketoprofen , Water Pollutants, Chemical , Anti-Bacterial Agents/analysis , Photolysis , Sulfonamides/chemistry , Sulfanilamide/analysis , Sulfamethoxazole/analysis , Water , Pharmaceutical Preparations , Water Pollutants, Chemical/analysis
18.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 07.
Article in English | MEDLINE | ID: mdl-38256908

ABSTRACT

Pulmonary inflammations such as chronic obstructive pulmonary disease and cystic fibrosis are widespread and can be fatal, especially when they are characterized by abnormal mucus accumulation. Inhaled corticosteroids are commonly used for lung inflammations despite their considerable side effects. By utilizing particle engineering techniques, a combined dry powder inhaler (DPI) comprising nanosized ketoprofen-embedded mannitol-coated microparticles was developed. A nanoembedded microparticle system means a novel advance in pulmonary delivery by enhancing local pulmonary deposition while avoiding clearance mechanisms. Ketoprofen, a poorly water-soluble anti-inflammatory drug, was dispersed in the stabilizer solution and then homogenized by ultraturrax. Following this, a ketoprofen-containing nanosuspension was produced by wet-media milling. Furthermore, co-spray drying was conducted with L-leucine (dispersity enhancer) and mannitol (coating and mucuactive agent). Particle size, morphology, dissolution, permeation, viscosity, in vitro and in silico deposition, cytotoxicity, and anti-inflammatory effect were investigated. The particle size of the ketoprofen-containing nanosuspension was ~230 nm. SEM images of the spray-dried powder displayed wrinkled, coated, and nearly spherical particles with a final size of ~2 µm (nano-in-micro), which is optimal for pulmonary delivery. The mannitol-containing samples decreased the viscosity of 10% mucin solution. The results of the mass median aerodynamic diameter (2.4-4.5 µm), fine particle fraction (56-71%), permeation (five-fold enhancement), and dissolution (80% release in 5 min) confirmed that the system is ideal for local inhalation. All samples showed a significant anti-inflammatory effect and decreased IL-6 on the LPS-treated U937 cell line with low cytotoxicity. Hence, developing an innovative combined DPI comprising ketoprofen and mannitol by employing a nano-in-micro approach is a potential treatment for lung inflammations.

19.
Drug Test Anal ; 16(3): 289-302, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37439283

ABSTRACT

Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post-drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3-hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3-hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vdss was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (-) ketoprofen, respectively. The mean half-life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (-) ketoprofen. Stimulation of ketoprofen-treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB2 , PGE2 , PGF2alpha , LTB4 , and 15(s)-HETE production for up to 120 h post-drug administration.


Subject(s)
Ketoprofen , Ketoprofen/analogs & derivatives , Horses , Animals , Ketoprofen/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal , Chromatography, Liquid , Calcium Ionophores , Lipopolysaccharides , Tandem Mass Spectrometry , Eicosanoids , Biomarkers
20.
ChemistryOpen ; 13(3): e202300147, 2024 03.
Article in English | MEDLINE | ID: mdl-37955865

ABSTRACT

A simple, sensitive and quick HPLC method was developed for the determination of ketoprofen in cell culture media (EMEM, DMEM, RPMI). Separation was performed using a gradient on the C18 column with a mobile phase of acetonitrile and miliQ water acidified by 0.1 % (v/v) formic acid. The method was validated for parameters including linearity, accuracy, precision, limit of quantitation and limit of detection, as well as robustness. The response was found linear over the range of 3-100 µg/mL as demonstrated by the acquired value of correlation coefficient R2=0.9997. The described method is applicable for determination of various pharmacokinetic aspects of ketoprofen in vitro.


Subject(s)
Ketoprofen , Ketoprofen/pharmacokinetics , Chromatography, High Pressure Liquid/methods , Indicators and Reagents
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