Ketoprofen Research Articles

Abietic acid antagonizes the anti-inflammatory effects of celecoxib and ketoprofen: Preclinical assessment and molecular dynamic simulations

The present work is designed to explore the anti-inflammatory properties of AA and its modulatory effects on celecoxib (CEL) and ketoprofen (KET) through in vitro, ex vivo, in vivo, and in silico approaches. Different concentrations of AA were utilized to evaluate the membrane-stabilizing potential via egg albumin and the Human Red Blood Cell (HRBC) denaturation model. In the animal model, formalin (50 μL) was injected into the right hind paw of young chicks to induce inflammation. AA was administered at 20 and 40 mg/kg (p.o.) to the experimental animals. We used CEL and KET as positive controls. The vehicle was provided as a control group. Two combinations of AA with CEL and KET were also investigated in all tests to assess the modulatory activity of AA. In addition, in silico investigation was used for predictions about drug-likeness, pharmacokinetics, and toxicity of the selected chemical compounds, and the study also evaluated the binding affinity, visualization, and stability of ligand-receptor interactions through molecular dynamic (MD) simulation. Results manifested that AA concentration-dependently significantly inhibited the egg albumin denaturation (IC50: 27.53 ± 0.88 μg/ml) and breakdown of HRBC (IC50: 15.69 ± 0.75 μg/ml), indicating the membrane stabilizing potential compared to the control group. AA also significantly (p < 0.05) lessened the frequency of licking and alleviated the paw edema in a dose-dependent manner in an in vivo test. However, AA reduced the activity of CEL and KET in combination treatment. AA showed good pharmacokinetic characteristics to be considered as a therapeutic candidate. Additionally, the in silico study displayed that AA demonstrated a relatively higher docking score of −9.1 kcal/mol with the cyclooxygenase-2 (COX-2) enzyme and stable binding in MD simulation. Whereas the standard ligand (CEL) expressed the highest binding value of −9.2 kcal/mol to the COX-2.

Computational exploration of novel ketoprofen derivatives: Molecular dynamics simulations and MM-PBSA calculations for COX-2 inhibition as promising anti-inflammatory drugs

Computer-aided drug design is widely employed to identify novel compounds for therapeutic applications. Ketoprofen (KTP), a commonly used and marketed nonsteroidal anti-inflammatory drug (NSAID), is effective in treating pain, fever, inflammation, and some cancers. In this research, we explored the behavior of six analogues designed by structurally modifying the KTP molecule. Specifically, KTP-A and KTP-B contain a –CN group at the ortho position, KTP-C and KTP-D have a –CN group at the meta position, and KTP-E and KTP-F feature a –CF3 group at the meta position. To assess these analogues, we conducted molecular dynamics simulations (MD) to study their inhibitory effects on human cyclooxygenase 2 (COX-2), providing detailed insights into the structure and dynamics of the protein both with and without ligands. MD simulation, enhanced by technological advances, has proven to be a powerful tool for new drug discovery. We further quantified the binding affinity of these drug molecules toward COX-2 using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations. The dynamic properties were evaluated through analyses of root mean square deviations (RMSD), root mean square fluctuations (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), covariance matrix, principal component analysis (PCA), and Gibbs free energy landscapes (FEL). Ultimately, this study confirms that the six KTP derivatives are promising candidates for the treatment of inflammation, with KTP-B standing out as particularly effective.

Piperine exerts anti-inflammatory effects and antagonises the properties of celecoxib and ketoprofen: in vivo and molecular docking studies

This study evaluates the anti-inflammatory effects of a natural product, piperine (PPN), using in vivo and in silico methodologies. In the in vivo segment, inflammation was induced in the right hind paw of young chicks via a formalin (50 μL) injection. PPN was orally administered at doses of 25 and 50 mg/kg with or without celecoxib (CXB) and/or ketoprofen (KPN) (42 mg/kg). The vehicle acted as the negative control group (NC). The in silico analysis predicted the drug-likeness, pharmacokinetics, and toxicity profile of PPN, along with evaluating its binding affinity and ligand-receptor interactions. Results indicate that PPN significantly (p < 0.05) reduced licking frequency and paw edoema in a dose-dependent manner. However, in combination therapy, PPN diminished the effects of both CXB and KPN. PPN showed high affinity (–8.6 kcal/mol) towards the COX-2 enzyme. Therefore, PPN exerts anti-inflammatory effects in chicks through COX-2 inhibition pathways and antagonises CXB and KPN activities.

Quality by Design (QbD) Approach to Develop Colon-Specific Ketoprofen Hot-Melt Extruded Pellets: Impact of Eudragit® S 100 Coating on the In Vitro Drug Release.

A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box-Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

Modulation of chondroprotective hyaluronic acid and poloxamer gel with Ketoprofen loaded transethosomes: Quality by design-based optimization, characterization, and preclinical investigations in osteoarthritis

Osteoarthritis (OA) is a chronic joint disease that results in biomechanical and morphological changes that contribute to cartilage degradation. Ketoprofen (KP), used in the treatment of OA, is a selective inhibitor of cyclooxygenase-2 (COX-2). Topical administration of KP bypasses gastric irritation as well as first-pass metabolism and increases localized delivery. The research intricates fabrication and optimization of KP-loaded transethosomes (KP-TEs) via Taguchi orthogonal array design and Central composite design (CCD). The optimized KP-TEs depicted an average vesicle size of 110.0 ± 1.70 nm, poly dispersibility index (PDI) of 0.103 ± 0.01, zeta potential −6.08 ± 0.27 mV, and conductivity of 0.049 ± 0.0001 mS/cm. The optimized KP-TEs were loaded in composite hyaluronic acid (HA) and poloxamer 407 (Px407) for an improvement of osteotrophic and chondroprotective transethosomal gel. The drug content of KP-TEs-HA/Px407 gel was found to be 90.08 ± 1.25 %. Preclinical research has been carried out by using the monosodium iodoacetate to develop model for osteoarthritis in male wistar rats. The X-ray imaging of KP-TEs-HA/Px407 gel treated group showed intact meniscus, healthy articular joint, and normal synovial lining same as the healthy control group. The IL − 1β IL-6, IL-22, TNF-α, and IL-10, levels, X-ray imaging, and studies on histopathology demonstrated the effectiveness of transethosomal gel in reducing pain and inflammation.

Novel drug-drug co-amorphous systems of olaparib with nonsteroidal anti-inflammatory drugs with improved solubility, physical stability, antitumor activity and pharmacokinetics

Olaparib (OLA), the first FDA-approved PARP inhibitor, has been approved successively for monotherapy or maintenance treatment of ovarian, breast and pancreatic cancer. Unfortunately, the poor solubility and bioavailability of OLA have limited its application. In this study, novel drug-drug co-amorphous systems of OLA with five nonsteroidal anti-inflammatory drugs (NSAIDs), including flurbiprofen (FLU), ketoprofen (KET), ibuprofen (IBU), diclofenac (DIC) or indomethacin (IND), were prepared for improving the aqueous solubility of OLA and achieving combination therapy against ovarian cancer. These new co-amorphous products were confirmed by powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Five co-amorphous systems were more soluble and released faster than the crystalline OLA in pH 6.8 buffer, and OLA-DIC and OLA-IND showed superior physicochemical stability under accelerated storage conditions. The antitumor activities of OLA-FLU, OLA-KET, OLA-IBU and OLA-DIC against OVCAR3 cell line were approximately increased by 3.5, 2.4, 2.7, and 6.0-fold than that of OLA, respectively. Moreover, pharmacokinetic studies of co-amorphous OLA-DIC in rats revealed that the OLA exhibited 6.14-fold improvement in AUC0-t value compared with crystalline OLA. Therefore, our study suggested that OLA-NSAIDs co-amorphous systems showed the great potentials to improve the solubility, dissolution behaviors, and bio-pharmaceutical performance of OLA.

The ability of UWWTP to remove NSAIDs: Impact on water quality in the Odra River Czech Republic concerning incoming European legislation

Increased consumption of pharmaceuticals has resulted in their detection in wastewater. If wastewater treatment plants (WWTPs) fail to eliminate these substances adequately, they can seep into the environment, posing potential risks. As non-steroidal anti-inflammatory drugs (NSAIDs) belong to the pharmaceuticals most frequently examined in wastewater, this study aimed to monitor wastewater from the municipal wastewater treatment plant in Ostrava (UWWTP) over the course of a year, specifically assessing how the presence of these substances in discharged wastewater could contaminate the Odra River. To further understand the impact of NSAIDs, we evaluated the effectiveness of UWWTP technology in removing the following selected drugs: diclofenac (DCF), ibuprofen (IBU), naproxen (NAP) and ketoprofen (KET) - as well as their main metabolites: 4′-hydroxydiclofenac (hydroxyDCF), carboxyibuprofen (carboxyIBU), desmethylnaproxen (desmethylNAP), and ketoprofen glucuronide (glucuronideKET).Wastewater samples were collected at both the inflow and outflow of the urban wastewater treatment plant (UWWTP) Ostrava from October 2022 to September 2023. The analysis was performed using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The concentrations of the monitored substances at the UWWTP inflow varied significantly, ranging from 79 ng/L to 112,125 ng/L, with the highest levels detected for ibuprofen (IBU), diclofenac (DCF), and their metabolites. The UWWTP demonstrated impressive treatment efficiency for IBU, exceeding 98%, while for DCF, it ranged between 56% and 87%. Building on these findings, a monitoring campaign was initiated along the Odra River to evaluate the concentrations of IBU and DCF - substances that had not been measured before. Water samples were taken from various locations along the Odra River from October to November 2023 and analyzed using the same methodology as the wastewater samples. The results indicate that, in line with the proposed environmental quality standards (EQS), IBU and DCF do not pose a significant contamination risk to the Odra River.

Enhancing ketoprofen's solubility and anti-inflammatory efficacy with safe methyl-β-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.

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.

Ecotoxicological study of seven pharmaceutically active compounds: Mixture effects and environmental risk assessment

Pharmaceutically active compounds (PhACs) have been detected in several aquatic compartments, which has been of environmental concern since PhACs can cause adverse effects on the aquatic ecosystem at low concentrations. Despite the variety of PhACs detected in surface water, ecotoxicological studies are non-existent for many of them, mainly regarding their mixture. In addition, water bodies can continuously receive the discharge of raw or treated wastewater with micropollutants. Thus, PhACs are subject to mixture and interactions, potentiating or reducing their toxicity. Therefore, the present study evaluated the toxicity on Aliivibrio fischeri of seven PhACs, which still needs to be explored in the literature. The effects were evaluated for the PhACs individually and for their binary and tertiary mixture. Also, the experimental effects were compared with the concentration addition (CA) and independent action (IA) models. Finally, an environmental risk assessment was carried out. Fenofibrate (FEN), loratadine (LOR), and ketoprofen (KET) were the most toxic, with EC50 of 0.32 mg L-1, 6.15 mg L-1 and 36.8 mg L-1, respectively. Synergistic effects were observed for FEN + LOR, KET + LOR, and KET + FEN + LOR, showing that the CA and IA may underestimate the toxicity. Environmental risks for KET concerning algae, and LOR e 17α-ethynylestradiol (EE2) for crustaceans and fish were high for several locations. Besides, high removals by wastewater treatment technologies are required to achieve the concentrations necessary for reducing KET and LOR risk quotients. Thus, this study contributed to a better understanding of the toxic interactions and environmental risks of PhACs.

Multiresponsive 4D Printable Hydrogels with Anti-Inflammatory Properties.

Multiresponsive hydrogels are valuable as biomaterials due to their ability to respond to multiple biologically relevant stimuli, i.e., temperature, pH, or reactive oxygen species (ROS), which can be present simultaneously in the body. In this work, we synthesize triple-responsive hydrogels through UV light photopolymerization of selected monomer compositions that encompass thermoresponsive N-isopropylacrylamide (NIPAM), pH-responsive methacrylic acid (MAA), and a tailor-made ROS-responsive diacrylate thioether monomer (EG3SA). As a result, smart P[NIPAMx-co-MAAy-co-(EG3SA)z] hydrogels capable of being manufactured by digital light processing (DLP) 4D printing are obtained. The thermo-, pH-, and ROS-response of the hydrogels are studied by swelling tests and rheological measurements at different temperatures (25 and 37 °C), pHs (3, 5, 7.4, and 11), and in the absence or presence of ROS (H2O2). The hydrogels are employed as matrixes for the encapsulation of ketoprofen (KET), an anti-inflammatory drug that shows a tunable release, depending on the hydrogel composition and stimuli applied. The cytotoxicity properties of the hydrogels are tested in vitro with mouse embryonic fibroblasts (NIH 3T3) and RAW 264.7 murine macrophage (RAW) cells. Finally, the anti-inflammatory properties are assessed, and the results exhibit a ≈70% nitric oxide reduction up to base values of pro-inflammatory RAW cells, which highlights the anti-inflammatory capacity of P[NIPAM80-co-MAA15-co-(EG3SA)5] hydrogels, per se, without being necessary to encapsulate an anti-inflammatory drug within their network. It opens the route for the fabrication of customizable 4D printable scaffolds for the effective treatment of inflammatory pathologies.

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.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

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.

Engineered beads-on-a-string nanocomposites for an improved drug fast-sustained bi-stage release

Nanocomposites represent one of the most useful strategies for resolving the pharmaceutical challenge about the dissolution and delivery of poorly water-soluble drugs. Besides the compatibility between the drug and polymeric carriers, the physical shapes of materials also play their important roles on the release behaviors of a guest poorly water-soluble drug from the host polymeric matrices. In this study, three kinds of nanocomposites in the forms of homogeneous nanofibers (E1), spindles-on-a-string (E2), and beads-on-a-string (E3) were prepared using electrospinning with ketoprofen (KET) as the model drug and a mixture of ethylcellulose (EC) and polyvinylpyrrolidone (PVP) as the polymeric matrices. Controllable preparation mechanisms of these morphologies are disclosed based on the results of SEM, TEM, and processes observations. XRD and FTIR data demonstrated that KET was compatible with PVP and EC. In vitro dissolution tests verified that all the three nanocomposites were able to provide the typical bi-stage fast-sustained release profiles of KET. Whereas, the beads-on-a-string E3 had a better functional performance than the spindles-on-a-string E2, and the homogeneous nanofibers E1 in terms of the KET sustained release profiles in the second stage. The protocols reported here pioneered a new way for developing novel functional nanocomposites based on the process-shape-performance relationship.

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.

Distinguishing the transitions of fluorescence spectra of tryptophan-134 and 213 in BSA induced by bindings of UV filters, oxybenzone-3, and avobenzone

Abstract Oxybenzone-3 (OBZ) and avobenzone (ABZ), commercially available ultraviolet-light filters for sunscreens, are known to induce photosensitizing allergy as an adverse effect, similar to an analgesic ketoprofen (KTP) due to their benzophenone moiety. The present study focused on OBZ and ABZ's protein binding compared to the related analgesics, KTP, diclofenac (DCF), and ibuprofen (IBP). The bovine serum albumin (BSA) was used as a protein model, measuring the fluorescent spectral peak shifts (i) and Stern–Volmer analysis (i) of its intrinsic tryptophans. Moreover, their adsorption types (iii) were verified using the singular value decomposition (SVD) computation of fluorescence spectra. For (i), (ii), and (iii), KTP and DCF caused a no-shift peak, an ordinary dynamic quenching, and a simple Langmuir adsorption. We found OBZ exhibiting (i) red-shift and (ii) including static quenching, ABZ suggesting (i) blue-shift and (iii) binding to multiple bind sites, and IBP indicating (i) blue-shift and (iii) multivalent bindings. Integrating the results, it can be understood that OBZ interacts with subdomain IA (around W134) in BSA, while ABZ interacts with subdomain IIA (around W213) in BSA. Moreover, IBP is bound to BSA with a cooperative effect, certified by Hill's plot. OBZ and ABZ had their individual binding sites on a protein, suggesting the exchange between OBZ and ABZ might reduce their own adverse effect. The present study verified the effectiveness of the SVD computation in distinguishing the details of the adsorption manner of ligands around the intrinsic fluorescent probes.

Synthesis and characterization of β-cyclodextrin polymers and its performance as a drug carrier

The aim of this study was to determine the optimal reaction conditions for the synthesis of hyperbranched cyclodextrin polymer (CDP) and to investigate their performance as drug carriers. In this study, β-Cyclodextrin (β-CD) was used as the basis for CDP nanocarriers, which were synthesized by reacting β-CD with pyromellitic dianhydride (PMDA) as a crosslinking agent. The effects of β-CD/PMDA molar ratio and reaction time were investigated to optimize the synthesis of CDP. The optimal reaction conditions were determined to be a reaction time of 2 h and a molar ratio of 1/12 β-CD/PMDA. Ketoprofen (KP) was used as a model drug to evaluate the loading capacity of CDP. The effects of KP/CDP (w/w) loading ratio, temperature, and stirring speed on the formation of the KP/CDP inclusion complex were investigated. The optimum conditions for loading KP into CDP were found to be 1/4 KP/CDP ratio, 4 h, 35 °C, and 300 rpm with a loading efficiency of 39.57%. Characterization of the CDP was performed using Zetasizer, FTIR, DSC, SEM and XRD analysis.

Randomized clinical trial of ketoprofen or ceftiofur for treatment of metritis in dairy cows

Our objectives were to compare the efficacy of ketoprofen or ceftiofur for treatment of metritis in dairy cows considering subsequent health, production, and reproduction. Cows from 2 commercial dairy farms in Ontario, Canada were examined with a Metricheck device 3 times per week from 2 to 14 d in milk (DIM). Cows with metritis (fetid vaginal discharge; n = 193) were blocked by parity and fever (rectal temperature ≥39.5°C or <39.5°C) and within each block per farm, randomly assigned to receive 3 mg/kg BW of ketoprofen (KET) or 2.2 mg/kg of ceftiofur hydrochloride (CEF), once a day for 3 d. Day of enrollment was considered study d 0. Rectal temperature and attitude were evaluated in cows with metritis on study d 0, 3, 4, 7, 10, and 13, and vaginal discharge was evaluated on study d 4, 7, 10, and 13. Body condition was scored at enrollment and 35 DIM, and serum concentration of haptoglobin was measured at d 0, 2, 4, and 7. Cows with rectal temperature ≥39.5°C or a depressed attitude on d 3 were classified as clinical failure and received treatment with ceftiofur for 3 d (KET), or 2 additional days (CEF), to a maximum of 5 d of treatment with ceftiofur. At 35 ± 3 DIM cows were examined for uterine involution by transrectal palpation, purulent vaginal discharge (PVD) by Metricheck, and endometritis by endometrial cytology. Time to onset of cyclicity was assessed by serum progesterone (P4) measurements at 28, 42, and 56 DIM. Contemporary cows from the same farms without metritis (NOMET; n = 1,043) were used for comparison. Data were analyzed with mixed linear or logistic regression or Cox's proportional hazard models, including herd as a random effect. The proportion of clinical resolution of metritis on d 3 (96% vs. 92%), of cows with fever (from d 3 to d 13 after enrollment) or fetid discharge (from d 4 to d 13 after enrollment), and the number of medical treatments (3.1 vs. 3.3) were not different between CEF and KET, respectively. Cows in KET received fewer antibiotic treatments than cows in CEF (0.3 vs. 3.1). Uterine involution, the prevalence of PVD (50% vs. 47%) and subclinical endometritis (6.6% vs. 4.3%), and the proportion of cyclic cows (82% vs. 86%) did not differ between CEF and KET. Cows in KET had greater serum haptoglobin concentration from d 2 to 7 after enrollment. The incidence of mastitis, lameness, or displaced abomasum to 60 DIM and subclinical ketosis to 21 DIM did not differ among CEF, KET, and NOMET. There were no differences in median days to first AI (CEF = 68 d; 95% CI: 65-70; KET = 69 d; 95% CI: 68-72; NOMET = 69 d; 95% CI: 68-70), and median days to pregnancy (CEF = 118 d; 95% CI: 92-145; KET = 113 d; 95% CI: 90-135; NOMET = 105 d; 95% CI: 101-109), pregnancy at first AI at 33 d after insemination (CEF = 42%; KET = 41%; NOMET = 41%), pregnancy loss after first AI (CEF = 8%; KET = 11%; NOMET = 8%), hazard of pregnancy or hazard of culling up to 300 DIM. Milk yield was not different between CEF and KET during the first 10 weeks, but lesser in KET at wk 2 and 4 and CEF at wk 2, 4, and 6 than in NOMET. In this pilot-scale study, given early detection, we did not detect differences in subsequent health, milk yield, or reproductive performance in cows with metritis initially treated for 3 d with CEF or KET. Additional, larger studies are warranted.

PLLA scaffolds functionalized with ketoprofen via rotary jet spinning for biomedical applications

Biopolymer-based biomaterials, such as poly (l-lactic acid) (PLLA), have long been recognized as scaffolds for drug delivery applications due to their advantages, including biodegradability and biocompatibility. Ketoprofen (KET) is a non-steroidal anti-inflammatory drug known for its analgesic properties. Despite its potential, more research is needed on the effective production of scaffolds functionalized with KET for biomedical applications. This study, therefore, aimed to develop PLLA-based carriers to transport KET obtained using Rotary Jet Spinning (RJS) and evaluate the influence of KET at different concentrations. RJS allowed PLLA-KET scaffold production with high productivity and uniform fiber morphology. KET particles dispersed in the PLLA fibers were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, the Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the presence of KET in the PLLA and that the crystalline structure of PLLA remained unchanged with the incorporation of KET, ensuring the material's structural integrity. Likewise, the thermogravimetric analysis showed the presence of KET affected the thermal stability of PLLA. Cell viability and confocal microscopy with preosteoblast cells demonstrated that PLLA-KET fibers maintained cell viability over time, indicating their compatibility with cell cultures, and revealed cell adhesion and distribution in the fibers varied with KET concentration. These results have significant implications, highlighting the potential use of PLLA-KET carriers in practical biomedical applications, such as drug delivery systems, bone implant devices, and dental applications, thereby advancing the field of biomaterials.

Pollution levels and ecological risks of PPCPs in water and sediment samples of Danjiangkou Reservoir.

The concentrations and distribution patterns of three typical pharmaceuticals and personal care products (PPCPs) in water and sediment samples obtained from Danjiangkou Reservoir during two seasonal sampling periods were studied to determine their impact on water quality. The temporal and spatial variations in concentrations measured were analyzed and related to ecological risks with data obtained during the mean-flow period (in June) and the dry period (in November). We found a high detection rate of ketoprofen (KTP) in water samples from Danjiangkou Reservoir; the concentrations ranged from not detected (ND) to 46.80ng/L with the highest values measured in the Hanku tributary samples followed by the samples collected in the main body of Danjiangkou Reservoir. The KTP concentrations in the Danku tributary samples were the lowest measured in this study. In addition, the concentrations of KTP in the Shending River, Sihe River, Jianghe River, Guanshan River, and Jianhe River water samples were relatively high in the mean-flow period. The water sample detection rates and concentrations of triclosan (TCS) and triclocarban (TCC) were low in both the mean-flow period and the dry period. All three kinds of PPCPs were detected in the sediment samples with the concentrations of KTP, TCS, and TCC ranging from 0.76 to 7.89μg/kg, 0.01 to 0.59μg/kg, and 0.01 to 11.36μg/kg, respectively. Overall, the concentrations of the three measured PPCPs in the water and sediment samples were all relatively low compared to results reported in the recent literature. The dry period concentrations of PPCPs in the water samples were lower than the concentrations measured in the mean-flow period. However, dry period concentrations were higher in the sediment samples compared to those in the mean-flow period samples. Our interpretation of the spatial and temporal patterns of PPCPs in Danjiangkou Reservoir suggests that these compounds were likely mainly derived from wastewater discharge in the upper reaches of the reservoir. The risk quotient (RQ) method was used for an ecological risk assessment of the detected PPCPs in this study. We found that TCS in water and sediment posed medium ecological risks to algae at different times of the year. In view of the extreme importance of water safety in Danjiangkou Reservoir, the ecological risks of PPCPs require additional attention.