Ketoprofen Research Articles

Novel chitosan oligosaccharide-based nanoparticles for gastric mucosal administration of the phytochemical "apocynin".

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here.Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul’s index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels.Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies.Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.

Combustion fabrication of magnetic porous carbon as a novel magnetic solid-phase extraction adsorbent for the determination of non-steroidal anti-inflammatory drugs

Based on a one-step combustion fabrication approach, a novel magnetic porous carbon (MPC) was fabricated using filter paper as porous carbon source and iron salts as magnetic precursors. The textural properties of the MPC were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), vibration sample magnetometer (VSM) and nitrogen absorption-desorption isotherms. The as-prepared MPC possessed a high specific surface area, a microstructure comprised of mesopores and strong magnetic response. It was employed as a magnetic solid-phase extraction (MSPE) adsorbent for the determination of three non-steroidal anti-inflammatory drugs (NSAIDs) in environmental water and biological samples coupled with high performance liquid chromatography (HPLC). The main parameters affecting extraction efficiency were investigated in detail and a satisfactory performance was obtained under the optimal conditions. The calibration curves were linear over the concentration ranging from 1 to 1200 μg L−1 for ketoprofen (KET) and 2–1200 μg L−1 for naproxen (NAP) and diclofenac (DCF) with determination coefficients (R2) between 0.9995 and 0.9997. The limits of detection (LODs) were in the range of 0.2–0.4 μg L−1. The intra- and inter-day relative standard deviations (RSDs) were less than 4.03% and 8.72%, respectively. The recoveries ranged from 84.67% to 113.73% with RSDs less than 7.76%. The satisfactory results confirmed the great potential of the novel MPC adsorbent for the extraction of NSAIDs from complex sample matrices.

Insights into pharmaceuticals removal in an anaerobic sulfate-reducing bacteria sludge system

In this study, we examined eight typical and widely detected pharmaceuticals (PhAs) removal in an anaerobic sulfate-reducing bacteria (SRB) sludge system (five antibiotics: sulfadiazine (SD), sulfamethoxazole (SMX), trimethoprim (TMP), ciprofloxacin (CIP) and enoxacin (ENO), and three nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), ketoprofen (KET) and diclofenac (DIC)). The results showed that the SRB sludge had the higher removal efficacy (20 to 90%) for antibiotics (SD, SMX, TMP, CIP and ENO) than NSAIDs (<20%) via adsorption and biodegradation under different operating conditions. Based on a series of batch studies, fluoroquinolone antibiotics (CIP and ENO) were instantly (<15 min) removed (∼98%) via adsorption on SRB sludge with adsorption coefficient (Kd) as high as 25.3 ± 1.8 L/g-suspended solids (SS). And thermodynamics results indicated that the adsorption of CIP and ENO on SRB sludge was spontaneous (Gibbs free energy change (ΔG°) <0 kJ/mol), exothermic (enthalpy change (ΔH°) <0 kJ/mol), and the adsorption process involved both physisorption and chemisorption (absolute value of ΔH° = 20 to 80 kJ/mol). Three widely prescribed antibiotics (SMX, TMP and CIP) were further investigated for their possible biodegradation pathways along with functional enzymes involved through a series of batch experiments. The biotransformation intermediates indicated that biotransformations of SMX and CIP in SRB sludge system could be initiated from the cleavage of isoxazole and piperazinyl rings catalyzed by sulfite reductase (SR) and cytochrome P450 (CYP450) enzymes, respectively. TMP was likely biotransformed via O-demethylation and N-acetylation coupled with hydroxylation reactions with CYP450 enzymes as the main functional enzymes. This study provided new insight into PhAs removal in SRB sludge system, and has significant potential of implementing sulfur-mediated biological process for the treatment of PhAs containing wastewater.

The Relationships between Process Parameters and Polymeric Nanofibers Fabricated Using a Modified Coaxial Electrospinning.

The concrete relationship between the process parameters and nanoproduct properties is an important challenge for applying nanotechnology to produce functional nanomaterials. In this study, the relationships between series of process parameters and the medicated nanofibers’ diameter were investigated. With an electrospinnable solution of hydroxypropyl methylcellulose (HPMC) and ketoprofen as the core fluid, four kinds of nanofibers were prepared with ethanol as a sheath fluid and under the variable applied voltages. Based on these nanofibers, a series of relationships between the process parameters and the nanofibers’ diameters (D) were disclosed, such as with the height of the Taylor cone (H, D = 125 + 363H), with the angle of the Taylor cone (α, D = 1576 − 19α), with the length of the straight fluid jet (L, D = 285 + 209L), and with the spreading angle of the instable region (θ, D = 2342 − 43θ). In vitro dissolution tests verified that the smaller the diameters, the faster ketoprofen (KET) was released from the HPMC nanofibers. These concrete process-property relationships should provide a way to achieve new knowledge about the electrostatic energy-fluid interactions, and to meanwhile improve researchers’ capability to optimize the coaxial process conditions to achieve the desired nanoproducts.

An insight into the adsorption of three emerging pharmaceutical contaminants on multifunctional carbonous adsorbent: Mechanisms, modelling and metal coadsorption

Pharmaceuticals (PhCs) are a specific group of emerging environmental contaminants, because there are designed to influence biochemical processes in non-target organisms even at low concentrations. In this study, phosphorised carbonaceous adsorbent (CScPA) was prepared from lignocellulosic biomass through thermochemical functionalisation. Phosphorus (P) doped microparticles were evaluated for the removal of emerging pharmaceutical contaminants such as sulfamethoxazole (SMX), carbamazepine (CBZ) and ketoprofen (KP) from aqueous solution. Characterisation of the adsorbent with the detailed mechanism study was carried out using pHpzc, SEM, BET, FTIR and XRD instruments. The influence of initial pH, adsorbent dose, contact time, initial pharmaceutical concentration and temperature on adsorption efficiency and capacity was evaluated in batch studies. CScPA exhibited excellent removal efficiency (≈99%) for all tested pharmaceuticals. According to FTIR results, the P containing groups showed obvious positive effects on pharmaceutical removal. The Langmuir isotherm (with maximal adsorption capacity of 19.181, 21.895 and 19.675 mg/g for SMX, CBZ, and KP, respectively) and the pseudo second-order kinetic model were suitable for describing the adsorption process. Adsorption mechanisms were mainly governed by π-π and n-π EDA interactions and H-bonds. It was demonstrated that presence of metal ions did not significantly influence pharmaceutical removal.

Acid-promoted Synthesis of MWCNT/UiO-66-NH2 Nanocomposite for Highly Efficient Removal of Ketoprofen

A novel MWCNT/UiO-66-NH2 nanocomposite with high porosity and water stability was fabricated through a facile acid-promoted method, which has high adsorption efficiency for ketoprofen (KET) from aq...

On-chip electromembrane extraction of acidic drugs.

In the present work, a new supported liquid membrane (SLM) has been developed for on-chip electromembrane extraction of acidic drugs combined with HPLC or CE, providing significantly higher stability than those reported up to date. The target analytes are five widely used non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), diclofenac (DIC), naproxen (NAX), ketoprofen (KTP) and salicylic acid (SAL). Two different microchip devices were used, both consisted basically of two poly(methyl methacrylate) (PMMA) plates with individual channels for acceptor and sample solutions, respectively, and a 25µm thick porous polypropylene membrane impregnated with the organic solvent in between. The SLM consisting of a mixture of 1-undecanol and 2-nitrophenyl octyl ether (NPOE) in a ratio 1:3 was found to be the most suitable liquid membrane for the extraction of these acidic drugs under dynamic conditions. It showed a long-term stability of at least 8 hours, a low system current around 20µA, and recoveries over 94% for the target analytes. NPOE was included in the SLM to significantly decrease the extraction current compared to pure 1-undecanol, while the extraction properties was almost unaffected. Moreover, it has been successfully applied to the determination of the target analytes in human urine samples, providing high extraction efficiency.

Monolayer and multilayer adsorption of pharmaceuticals on activated carbon: Application of advanced statistical physics models

In this paper, the advanced statistical physics models (ASPM) were used to provide reasonable interpretations of the adsorption of pharmaceuticals Ketoprofen (KTP) and Ibuprofen (IBP) on raw and ultrasound activated carbons. Monolayer and multilayer models were selected to explain the adsorption mechanisms of these pharmaceuticals. Based on the values of the captured pharmaceutical molecules (n), it was concluded that multi-molecular (n > 1) and multi-docking (n < 1) processes were possible for IBP and KTP adsorption on AC and UAC. A detailed thermodynamic analysis was performed demonstrating that the adsorption mechanism was endothermic and associated to physical forces. The thermodynamic analysis confirmed the feasibility and spontaneous nature of the adsorption of these pollutants on tested adsorbents.

Simultaneous determination of non-steroidal anti-inflammatory drugs and natural estrogens in the mussels Mytilus edulis trossulus

In this study, an ASE (Accelerated Solvent extraction)-SPE (Solid Phase Extraction)-GC/MS(SIM) method for the simultaneous determination of five non-steroidal anti-inflammatory drugs (NSAIDs: ibuprofen (IBU), paracetamol (PAR), diclofenac (DIC), naproxen (NAP) and ketoprofen (KET)) and three natural estrogens (estrone (E1), 17β-estradiol (E2), estriol (E3)) in mussels was proposed, which is simple, cheap and easy for use in environmental laboratories. For the first time, the sorbents: PSA (Primary Secondary Amine) and FLORISIL®, placed directly inside the extraction cells, were used for the improvement of the ASE procedure for the isolation of these pollutants from mussel samples. The application of FLORISIL® especially allowed the purification of the extract to increase recovery, without the loss of analytes, or prolongation of the extraction time. The proposed ASE-SPE-GC/MS(SIM) method was validated (the method detection limit values were in the range of 1 ng/g dry weight (d.w.) for IBU to 7 ng/g d.w. for E1; the measurement intermediate precision was between 0.24% and 7.85%; the mean recovery was in the range of 80–118%) and used for the determination of NSAIDs and estrogenic hormones in whole tissue of the mussels Mytilus edulis trossulus collected from the Gulf of Gdansk (southern Baltic Sea). IBU, NAP, DIC and E1 were determined in these samples; however, the pharmaceuticals were found only in smaller (with a length of 2–3 cm) individuals. The observed differences in the concentrations of CEC in smaller and older mussel organisms were fully discussed. Summarizing, this method could be used for monitoring these CEC in such organisms in order to expand our knowledge of their influence on the water ecosystem, however, in such investigations smaller mussel organisms should be used.

Surface functionalised adsorbent for emerging pharmaceutical removal: Adsorption performance and mechanisms

А highly effective adsorbent (PPhA) was designed using “acid catalyst” functionalisation and tested for six emerging PhCs (sulfamethoxazole (SMX), carbamazepine (CBZ), ketoprofen (KP), naproxen (NPX), diclofenac (DCF) and ibuprofen (IBF)) in a batch study. Characterisation results (BET, SEM, FTIR, XRD and pHzpc) showed that the functionalisation process generates a microporous material with a multitude of new functional groups (such as phosphate and phosphonate) present on the surface. Adsorption capacity reached near maximum within 10 min while equilibrium was obtained in 60 min. Findings suggest that the mass transfer was governed mainly by intraparticle diffusion processes through formation of H-bonds, π–π and n–π electron donor–acceptor interactions. A pH influence study showed that electrostatic interactions played a minor role in the overall removal mechanism. The magnitude of E was <8 kJ mol−1 for all studied PhCs, indicating that adsorption is mainly due to physisorption. Equilibrium data were best represented by the Freundlich model and the theoretical monolayer adsorption capacities were 17.193, 17.685, 19.265, 17.657, 21.116 and 23.332 mg g−1 for SMX, CBZ, KP, NPX, DCF and IBF, respectively. Based on these results, this PPhA is proposed as an excellent adsorbent for PhC removal.

Evaluation of pH- responsive poly(styrene-co-maleic acid) copolymer nanoparticles for the encapsulation and pH- dependent release of ketoprofen and tocopherol model drugs

The pH- induced intelligent drug release ability of poly(styrene-co-maleic acid) copolymer nanoparticles (SMA NPs; d = 22.4 ± 3.1 nm) is presented using poorly water soluble ketoprofen (KETO) and α-Tocopherol (TP) model drugs. Increasing styrene content of the copolymer led to lower surface charge (from −28.4 to −15.0 meq/100 g) and the different styrene/maleic acid ratio (SMA#1: 1:2; SMA#2: 2:1 and SMA#3: 3:1) influences the pH- dependent solubility properties. Because of the polyanionic nature, homogeneous polymer solution was obtained at higher pH, while at lower pH nanoparticles were formed. The corresponding cut- off pH values showed increasing tendency with increasing hydrophobicity (pH = 3.12, 4.22 and 5.44 for SMA#1, 2 and 3, respectively).Next the hydrophobic, non- water soluble KETO and TP drug cores were coated with SMA#2 shell. The polymer-stabilized drug particles provided stable dispersion in aqueous environment, i.e. the prepared polymer shell increased the water dispersibility of the initial hydrophobic drugs. According to the experiments the release of low crystallinity KETO drug was almost complete at physiological pH (=7.40), while at acidic pH the released amount of model drug was only about 30%. Similar kinetic release profile was obtained in the case of more hydrophobic TP drug without charged groups and it indicates that the drug release was primarily controlled by the pH- responsive polymer particles instead of the pH- dependent solubility of the model drug. The prepared NPs could be useful in all areas where the alkaline pH value causes problems, for example in the case of female genital diseases of fungal origin.

Facile synthesis and light-induced antibacterial activity of ketoprofen functionalized bacterial cellulose membranes

Bacterial cellulose (BC) has already attracted tremendous interests from researchers especially those working in the area of functional nanomaterials. In this work, the chemical grafting of BC with ketoprofen (KP) was performed through eco-friendly and simple SolReact method. Surface functionalization of BC was confirmed by FTIR, XRD, XPS, TG, SEM, and TEM. Meanwhile, the stress-strain and water contact angle were also measured simultaneously. The results showed that surface functionalization was achieved under the mild reaction condition. The three-dimensional (3D) microstructure and crystalline structure of BC were maintained without being destroyed. The thermal stability of BC-KP was improved while retaining hydrophilic property and mechanical property. The photochemical property of BC-KP showed that the ROS generation was positively correlated with the time of light irradiation. The results of antibacterial tests on E.coli and S.aureus showed that the BC-KP possessed best antibacterial performance after 30 min UVA light irradiation, reaching to 72.7% and 81.6%, respectively. SEM studies displayed the cell morphology changed and membrane damaged resulting from the ROS produced under the light irradiation, which was a potential approach to prevent the bacteria resistance to conventional antibiotics. The antibacterial BC-based membranes grafting with photodynamic antimicrobial agents may be utilized as an efficient healthcare product for prevention of infectious disease.

Effects of selected nonsteroidal anti-inflammatory drugs on acute-phase protein levels after dehorning in Holstein heifers

The purpose of this study was to evaluate the effects of ketoprofen (KTP), flunixin meglumine (FLM), and meloxicam (MLX) administration on acute-phase proteins after dehorning in Holstein heifers. A total of 21 Holstein heifers were enrolled into three groups of equal size (n=7) and administered ketoprofen, flunixin meglumine, or meloxicam, at doses of 2.2 mg/kg, 1.1 mg/kg, and 1 mg/kg body weight, respectively. Serum amyloid A, haptoglobin, and ceruloplasmin levels were determined before the administration of the three drugs (0 hrs) and at 6, 12, 24, 48, and 96 hours post-administration. The mean values (±SD) obtained revealed no significant alteration in APP levels at 0 hrs in any of the three groups. Time-dependent alterations, however, were significant in all groups. Group-time interactions were significant (P &lt; 0.001) for ceruloplasmin concentrations, whereas results for serum amyloid A and haptoglobin levels were deemed non-significant. Inter-group interaction revealed no significant findings regarding serum amyloid A and ceruloplasmin levels, but haptoglobin levels showed a significant difference between the KTP and FLM groups at 48 hrs. It may therefore be reasonably suggested that KTP, FLM, and MLX could all be administered to effect slight changes in acute phase proteins.

(S)-1-(1-Methylpyridin-2-yl)-3-aminopiperidine as a novel derivatization reagent capable of enantiomeric separation and enhanced ESI-MS/MS detection for chiral carboxylic acids

A novel derivatization reagent, (S)-1-(1-methylpyridin-2-yl)-3-aminopiperidine (MPAPp), was designed and developed for the enantiomeric separation by conventional reversed-phase liquid chromatography (LC) and the sensitive electrospray ionization-tandem mass spectrometry (ESI-MS/MS) detection of chiral carboxylic acids. MPAPp reacted with the carboxylic acids at 60 °C within 5 min in the presence of a condensation agent to produce the positively-charged and diastereomeric derivatives. The MPAPp-derivatization enabled the satisfactory enantiomeric separation not only of the α- and β-chiral carboxylic acids [ketoprofen (KET), etodolac and 3-hydroxypalmitic acid], but also of the γ-chiral carboxylic acid [2-(γ-carboxyethyl)-6-hydroxy-2,7,8-trimethylchroman (γ-CEHC)] with the resolution (Rs) values of 1.35–1.82. The derivatization also worked for the enantiomeric separation of the ε-chiral carboxylic acid [α-lipoic acid, separation factor (α) = 1.04]. The detection responses of the MPAPp-derivatives were 25–500-times greater than the intact carboxylic acids, therefore, the low femtomolar derivatives were fully detected. The trace detection of a γ-CEHC enantiomer (limit of detection, 1.9 fmol on column) in saliva was achieved by the MPAPp-derivatization followed by LC/ESI-MS/MS. The pharmacokinetic profiles of the KET enantiomers during/after the MOHRUS® patch application were also obtained from the saliva analysis using the MPAPp-derivatization based LC/ESI-MS/MS method, which was precise (intra- and inter-assay relative standard deviations, <6.6% and <4.6%, respectively) and accurate (96.2–105.3%) within the range of 35–280 pg/mL for each enantiomer.

Applied of central composite design for the optimization of removal yield of the ketoprofen (KTP) using electrocoagulation process

ABSTRACTIn this paper, the modeling and the optimization of the removal efficiency of ketoprofen (KTP) by the electrocoagulation process were studied. The central composite design experiments (CCD) method was used to study the main effects and the interaction effects between operational parameters and to optimize the value of each parameter. According to the regression equation obtained, the current density appears to be one of the most important parameters (b2 = +22.11) controlling the removal efficiency of KTP. The positive sign of b2 coefficient suggests that the increase of current density increases the yield of removal. The second significant parameter with a negative effect was the initial KTP concentration (b3 = −16.27). This result suggests that the removal efficiency was inversely proportional to the initial concentration. In addition, according to the model, the most influencing interactions were pH-current density, pH-initial concentration, and current density-initial concentration. The model obtained by CCD led to the following optimal conditions for KTP removal efficiency (96.70%): pH = 7, i = 24.04 mA cm−2, and C0 = 5 mg L−1.

MOLECULAR MECHANISMS OF POTENTIAL SYNERGI STIC EFFECT OF KETOPROFEN AND MELOX ICAM WITH CONVENTION AL CYTOSTATICS IN HUMAN CERVIX CANCER CELL LINE

Cyclooxygenases clearly appear to be implicated in carcinogenesis. It has been reported that COX-2 is active throughout the entire process of cancer development and progression. Various molecular mechanisms may be responsible for this. Epidemiological and experimental studies have revealed that nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the risk of cancer. Inhibition of COX provides a plausible explanation of the data on NSAIDs and cancer. However, the molecular pathways of this effect are still unclear, more complex and likely involve multiple COX-2-dependent and independent mechanisms, where pro- and anti-apoptotic Bcl-2 family members may take part. We examined the effects of ketoprofen (KT), as nonselective COX-1/2, and meloxicam (MK), as selective COX-2 inhibitor, alone and combined with 5-fluorouarcil (FU) and cisplatin (CP), on the proliferation by MTT test and Bcl-2/Bax expression in HeLa cells (human cervical carcinoma cells). MC alone or combined with conventional anticancer drugs, FU and CP, showed better cytotoxic and antiproliferative effect than KT. The levels of Bcl-2 were decreased while the levels of Bax were increased dose-dependently by KT and MC. A significant increase in the expression of Bax protein in HeLa cells was more pronounced for MC. The synergy observed in the effects of ketoprofen and meloxicam with cisplatin and 5-fluorouracil on the cervical cancer cell line was generated by an enhancement of apoptosis. Therefore, ketoprofen and meloxicam may represent therapeutic candidates to improve access of cervical cancer chemoprevention and chemotherapy.

Use of Meloxicam or Ketoprofen for Piglet Pain Control Following Surgical Castration.

Surgical castration of piglets is performed routinely on commercial pig farms, to prevent boar taint and minimize aggression. While this procedure is known to be painful, piglets are generally not provided any analgesic for pain relief, leading to welfare concerns. The objectives of this study were to assess the efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (MEL) (0.4 mg/kg or 1.0 mg/kg) and ketoprofen (KET) (6.0 mg/kg) in reducing behavioral indicators of pain in castrated piglets. This study also examined the utility of the Piglet Grimace Scale (PGS) as a pain assessment tool. Nineteen litters of 5-days-old male piglets (n = 120) were used and piglets within a litter were randomly assigned to one of eight possible treatments: 0.4 mg/kg MEL-castrated or uncastrated, 1.0 mg/kg MEL-castrated or uncastrated, 6.0 mg/kg KET-castrated or uncastrated, saline (castrated control), or sham (uncastrated control). Treatments were administered intramuscularly (IM) 20 min prior to surgical castration. Piglets were video recorded for 1 h pre-procedure, for 8 h immediately post-castration and for another hour, 24 h post-procedure. Twenty-one behaviors and postures were scored continuously for the first 15 min of each hour and 1,156 still images of piglet faces were collected and scored using the PGS. Within each treatment group post-castration, castrated piglets displayed significantly more pain-related behaviors than uncastrated piglets (0.4 mg/kg MEL: p = 0.0339, 1.0 mg/kg MEL: p = 0.0079, 6.0 mg/kg KET: p = 0.0034, Controls: p < 0.0001). Castrated piglets also grimaced significantly more post-procedure than uncastrated piglets (p = 0.0061). Compared to the castrated control, none of the NSAID treatments significantly reduced piglet pain behaviors (0.4 mg/kg MEL: p = 1.0000, 1.0 mg/kg MEL: p = 0.9995, 6.0 mg/kg KET: p = 0.4163) or facial grimacing. Piglets demonstrated significantly more pain behaviors 24 h post-castration than at all other time points (p < 0.0001). The PGS was a less effective measure to detect acute pain; however, our findings suggest it does have utility as a pain assessment tool in neonatal pigs. Our findings also indicate that the use of these NSAIDs were ineffective at alleviating castration-associated pain in piglets.

Dissolution improvement of an active pharmaceutical ingredient in a polymer melt by hot melt extrusion

Abstract Dissolution of poorly water-soluble active pharmaceutical ingredients (APIs) in polymeric melts plays an important role in the manufacturing of solid dispersions and solid solutions. The understanding of the dissolution is essential for selecting the processing equipment, the operating conditions, and the polymer excipients. The methodology presented in this work for ketoprofen (KTO) and polymer excipients serves as a screening process to select the best API-polymer formulation for hot melt extrusion (HME) to target a specific release profile. KTO dispersion within the polymer was characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and dissolution tests. Thermal characterization shows that a single phase amorphous solid solution (one glass transition temperature [Tg]) was achieved under the HME processing conditions and screw configuration; and with the combination of polymer excipients, an extended release profile of KTO was accomplished, releasing 100% of KTO in 24 h.

A new laccase-mediator system facing the biodegradation challenge: Insight into the NSAIDs removal

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely found pollutants in the aquatic environment and the currently available treatments for their removal are usually associated with some drawbacks. The aim of this research was to apply a laccase-mediator system for the degradation of some commonly used NSAIDs, namely diclofenac (DCF), naproxen (NAP) and ketoprofen (KP). The biocatalyst was obtained by direct immobilization on chitosan beads of a periodate-oxided laccase from Trametes versicolor. A preliminary study aimed to optimize DCF degradation in the presence of 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonicacid) diammonium salt (ABTS) as mediator. It turned out that pH 3 and a 1:1 M ratio for ABTS:drug were the best experimental conditions under which DCF was degraded at 90% after 3 h. In addition, an efficient reuse of the biocatalyst for up to 5 cycles emerged. DCF was further mixed with naproxen and ketoprofen to test whether laccase was still able to eliminate DCF and eventually act on the other compounds. At just 0.02 U of laccase activity, diclofenac was completely degraded within 3 h, while an almost complete removal for naproxen (∼90%) and a partial removal for ketoprofen (30%) occurred in 7 d when drugs were added at high concentrations (78.5 μM, 98 μM and 108 μM, respectively). After 7 d of degradation, transformation products of diclofenac, identified as hydroxylated compounds, disappeared. Naproxen products were, instead, reduced to very small amounts.

Ketoprofen affects the mammary immune response in dairy cows in vivo and in vitro

Nonsteroidal anti-inflammatory drugs are commonly administered parenterally in addition to antimicrobial mastitis therapy to increase the well-being of the diseased animal. As mastitis is usually a localized infection of mammary tissue, we tested the hypothesis that a local administration of nonsteroidal anti-inflammatory drugs through the teat canal could have anti-inflammatory effects on the affected area. We investigated the effects of intramammarily administered ketoprofen (KET) during an LPS-induced immune response on somatic cell count (SCC) and blood-milk barrier integrity. In addition, we investigated the effects of KET on the mRNA abundance of immune factors and their prostaglandin E2 secretion in primary bovine mammary epithelial cells in vitro. Six cows received 0.2 µg of LPS (serotype O26:B6) together with 50 mg of KET into one quarter and LPS only in the opposing quarter. The increase of SCC and of serum albumin (SA) and IgG concentrations and the increase of lactate dehydrogenase (LDH) activity in milk induced by LPS were lower in quarters that received KET in addition. In 3 cows, intramammary KET (50 mg) without additional LPS did not affect SCC, SA, IgG, and LDH in milk. Effects of KET on the immune response of mammary epithelial cells in vitro were investigated in cells from 3 cows challenged with or without LPS (0.2 µg/mL) and with or without additional KET in 2 concentrations (1.25 or 2.5 mg/mL). Ketoprofen reduced the LPS-induced increase of mRNA abundance of tumor necrosis factor α, IL-8, serum amyloid A, and cyclooxygenase-2. The mRNA abundance of cyclooxygenase-1 and prostaglandin E synthase was reduced in cells without LPS challenge by addition of KET at 2.5 mg/mL. Furthermore, the LPS-induced secretion of prostaglandin E2 of mammary epithelial cells into the supernatant could not be detected if KET was added. The results demonstrate that intramammary KET diminishes the increase of SCC and reduces the impairment of the blood-milk barrier (based on SA and LDH in milk), leading to a reduced IgG concentration in milk during LPS-induced mastitis. In mammary epithelial cells, KET limits the expression of several immune factors that are increased during an immune response. In summary, intramammary administration of KET reduces the inflammatory response in the mammary gland. However, it remains unclear whether the inhibited transfer of immune cells and IgG from blood into milk after KET administration would reduce the success of the immune defense in infectious mastitis.