Ozonolysis of ketoprofen in polluted water: Reaction pathways, kinetics, removal efficiency, and health effects.

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.

Effect of post-mating administration of ketoprofen on serum progesterone concentration and fertility in Akkaraman ewes.

A major cause of early embryonic losses is inadequate secretion of progesterone (P4) hormone due to luteal insufficiency in farm animals. Post-mating applications that directly or indirectly increasing serum P4 concentrations have a positive effect on fertility. The aim of this study was to investigate the effect of post-mating administration of ketoprofen on serum P4 concentration and fertility in Akkaraman ewes synchronized with a short-term protocol during the breeding season. Oestrus monitoring ewes after synchronization were hand-mated and randomly assigned to two equal groups (Ketoprofen vs. Control). Ewes in the ketoprofen group (KPG) (n = 40) were administered with ketoprofen (Rifen, Richter pharma, Austria) intramuscularly (im) at a dose of 3 mg/kg on days 9 and 10 after mating. In the control group (CG) ewes (n = 40) were administered with saline im on the same days. Blood samples were collected from ewes in both groups at four different time points of post-mating days (9, 12, 15 and 18 days). The results showed that there were no statistical differences between the KPG and CG groups on fertility parameters; pregnancy rates (85% vs. 72.5%), lambing rates (100% vs. 100%), single birth rates (55.9% vs. 55.2%), multiple birth rates (44.1% vs. 44.8%), litter sizes (1.56 vs. 1.55). In pregnant ewes, serum P4 concentrations on day 18 (4.35 ± 0.34 ng/mL) in the KPG group were higher than (3.27 ± 0.27 ng/mL) in CG group (P < 0.05). It was concluded that post-mating ketoprofen administration have no significant effect on fertility, but significantly increased the serum P4 concentration on day 18 in pregnant ewes.

Surprising results of patch testing with the baseline series in patients with photocontact allergy to ketoprofen.

OBJECTIVE: Photoallergic reactions due to topical ketoprofen are common. As some simultaneous contact allergies have been described in the literature, we aimed to get an overview of the pattern of reactivity towards common allergens in the baseline series in ketoprofen-photoallergic individuals. METHODS: Using our database, we found 94 patients with photocontact allergy to ketoprofen diagnosed during 1999-2018. Approximately 12 800 patients patch tested with the baseline series during the same time frame served as controls. Data on patch testing with the baseline series of 518 individuals belonging to the general population were obtained from an earlier study, and a comparison of allergy rates was made with the ketoprofen group. RESULTS: Contact allergy to fragrance mix I and Myroxylon pereirae was overrepresented among patients with photocontact allergy to ketoprofen (42.3% vs. 6.6% and 47.9% vs. 6.6%, p < 0.001, respectively). Significant overrepresentation was also shown for 4-tert-butylphenolformaldehyde resin (PTBP-F-R), phenol formaldehyde resin (PFR-2), black rubber mix, budesonide (all p < 0.001), and fragrance mix II (p = 0.02). The pattern was similar, but with lower significance levels for fragrance mix II and budesonide, regardless of whether or not the individuals had been photopatch tested because of a suspected photoallergic contact dermatitis from ketoprofen. CONCLUSION: Contact allergy to fragrance mix I, Myroxylon pereirae, black rubber mix, PFR-2, PTBP-FR, and to a somewhat lower extent, to fragrance mix II and budesonide, is common in individuals photoallergic to ketoprofen. It remains to be seen whether sensitisation to ketoprofen leads to simultaneous sensitisation to a number of other, chemically non-related, substances.

Enhancing ketoprofen's solubility and anti-inflammatory efficacy with safe methyl-ß-cyclodextrin complexation.

Improved solubility and anti-inflammatory (AI) properties are imperative for enhancing the effectiveness of poorly water-soluble drugs, particularly non-steroidal anti-inflammatory drugs (NSAIDs). To address these critical issues, our focus is on obtaining NSAID materials in the form of inclusion complexes (IC) with methyl-beta-cyclodextrin (MCD). Ketoprofen (KTP) is selected as the NSAID for this study due to its potency in treating various types of pain, inflammation, and arthritis. Our objective is to tackle the solubility challenge followed by enhancing the AI activity. Confirmation of complexation is achieved through observing changes in the absorbance and fluorescence intensities of KTP upon the addition of MCD, indicating a 1:1 stoichiometric ratio. Phase solubility studies demonstrated improved dissolution rates after the formation of ICs. Further analysis of the optimized IC is conducted using FT-IR, NMR, FE-SEM, and TG/DTA techniques. Notable shifts in chemical shift values and morphological alterations on the surface of the ICs are observed compared to their free form. Most significantly, the IC exhibited superior AI and anti-arthritic (AA) activity compared to KTP alone. These findings highlight the potential of ICs in expanding the application of KTP, particularly in pharmaceuticals, where enhanced stability and efficacy of natural AIs and AAs are paramount.

Design and evaluation of a drug-in-adhesive patch for the transdermal delivery of ketoprofen.

The purpose of this study was to design a drug-in-adhesive (DIA) patch for transdermal delivery of ketoprofen, using hot-melt pressure-sensitive adhesive as the matrix of the patch. The adhesion properties and skin permeation of the patches were examined, and in vivo pharmacokinetics and tissue distribution of patches were evaluated. The novel ketoprofen patch with high adhesion was prepared by holt-melt method. The effects of different percentages of L-menthol on in vitro permeation were screened, 3% was added as the amount of permeation enhancer and the 24 h cumulative permeation amount(277.46 ± 15.58 µg/cm2) comparable to that of commercial patch MOHRUS®(279.74 ± 29.23 µg/cm2). Pharmacokinetic and the tissue distribution study showed no matter in plasma, muscle or skin, the drug concentration of self-made ketoprofen patch was equivalent to that of commercial patch. These data indicated that the self-made patch provided a new reference for the development of ketoprofen dosage forms and promising alternative strategy for analgesic treatment.

A facile colorimetric sensor for ketoprofen detection in milk: Integrating molecularly imprinted polymers with Cu-doped Fe3O4 nanozymes.

A facile and efficient detection method is required to address the potential health risks of ketoprofen (KP) in animal-derived foods. Herein, we integrated molecularly imprinted polymers (MIPs) with Cu-doped Fe3O4 nanozymes (Fe3O4-Cu) to develop a selective colorimetric sensor for KP detection. Chitosan and glutaraldehyde were used as functional monomers and cross-linkers to fabricate proposed the MIPs@Fe3O4-Cu. On KP addition, it was specifically captured by the imprinted cavities, thereby blocking the channels between chromogenic substrates and Fe3O4-Cu. Based on this rationale, a selective colorimetric sensor utilizing MIPs@Fe3O4-Cu was established, exhibiting a linear range of 0.25-100 µM and a detection limit of 0.073 µM. The developed method was validated through its application in milk samples, yielding satisfactory recoveries with low relative standard deviations. This efficient and selective colorimetric sensor holds immense significance for KP detection in complex samples.

The effects of ketoprofen and meloxicam on oxidative stress through the glutathione pathway after ketamine-xylazine anesthesia and ulcer induction in rats: A comparative study.

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.

Photopatch testing: Clinical characteristics, test results, and final diagnoses from the North American Contact Dermatitis Group, 2009-2020.

BACKGROUND: Photoallergic contact dermatitis (PACD) is a delayed hypersensitivity reaction to allergens only in the presence of ultraviolet radiation in sunlight. Photopatch testing (PhotoPT) is necessary to confirm the diagnosis of PACD. There are few published studies of PhotoPT in North America. OBJECTIVE: To summarise the results of patients photopatch tested by members of the North American Contact Dermatitis Group (NACDG), 2009-2020. METHODS: Retrospective analysis of patient characteristics and PhotoPT results to 32 allergens on the NACDG Photopatch Test Series. RESULTS: Most of the 454 tested patients were female (70.3%), 21-60 years old (66.7%) and White (66.7%). There were a total of 119 positive photopatch tests. Sunscreen agents comprised 88.2% of those, with benzophenones responsible for over half of them. Final diagnoses included PACD in 17.2%, allergic contact dermatitis (ACD) in 44.5%, polymorphous light eruption (PMLE) in 18.9% and chronic actinic dermatitis (CAD) in 9.0% of patients. CONCLUSIONS: In 454 patients with suspected photosensitivity referred for photopatch testing in North America, approximately one-fifth had PACD. Sunscreen agents, especially benzophenones, were the most common photoallergens. Other common diagnoses included ACD, PMLE and CAD. Photopatch testing is an important tool for differentiating these conditions.

Preparation of microspheres with sustained ketoprofen release by electrospray for the treatment of aseptic inflammation.

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.

Evaluation and analysis of the adsorption mechanism of three emerging pharmaceutical pollutants on a phosphorised carbon-based adsorbent: Application of advanced analytical models to overcome the limitation of classical models.

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.

Templated Nucleation of Clotrimazole and Ketoprofen on Polymer Substrates.

The use of different template surfaces in crystallization experiments can directly influence the nucleation kinetics, crystal growth, and morphology of active pharmaceutical ingredients (APIs). Consequently, templated nucleation is an attractive approach to enhance crystal nucleation kinetics and preferentially nucleate desired crystal polymorphs for solid-form drug molecules, particularly large and flexible molecules that are difficult to crystallize. Herein, we investigate the effect of polymer templates on the crystal nucleation of clotrimazole and ketoprofen with both experiments and computational methods. Crystallization was carried out in toluene solvent for both APIs with a template library consisting of 12 different polymers. In complement to the experimental studies, we developed a computational workflow based on molecular dynamics (MD) and derived descriptors from the simulations to score and rank API-polymer interactions. The descriptors were used to measure the energy of interaction (EOI), hydrogen bonding, and rugosity (surface roughness) similarity between the APIs and polymer templates. We used a variety of machine learning models (14 in total) along with these descriptors to predict the crystallization outcome of the polymer templates. We found that simply rank-ordering the polymers by their API-polymer interaction energy descriptors yielded 92% accuracy in predicting the experimental outcome for clotrimazole and ketoprofen. The most accurate machine learning model for both APIs was found to be a random forest model. Using these models, we were able to predict the crystallization outcomes for all polymers. Additionally, we have performed a feature importance analysis using the trained models and found that the most predictive features are the energy descriptors. These results demonstrate that API-polymer interaction energies are correlated with heterogeneous crystallization outcomes.

Parental (F0) exposure to Cadmium and Ketoprofen induces developmental deformities in offspring (F1): A transgenerational toxicity assessment in zebrafish model.

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.

Ketoprofen promotes the conjugative transfer of antibiotic resistance among antibiotic resistant bacteria in natural aqueous environments.

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.

Modeling the Structure of Ketoprofen-Poly(vinylpyrrolidone) Amorphous Solid Dispersions with Empirical Potential Structure Refinements of X-ray Scattering Data.

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.

Microemulsion-Based Polymer Gels with Ketoprofen and Menthol: Physicochemical Properties and Drug Release Studies.

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.

Cadmium and ketoprofen accumulation influences aquatic ecosystem demonstrated using in-vivo zebrafish model.

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.

Comparison of the effect of dexamethasone, ketoprofen and cold compress on postoperative quality of life following impacted lower third molar surgery: a randomized clinical trial.

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.

Modified Release 3D-Printed Capsules Containing a Ketoprofen Self-Nanoemulsifying System for Personalized Medical Application.

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.

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

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.