Pollution of the environment with inorganic and organic substances is one of the main problems in the world. For this reason, it is necessary to conduct researches for effective methods of biodegradation of xenobiotics, including drugs whose unmetabolized forms are introduced into the environment, especially into water. One possible solution to this problem may be the use of white rot fungi, such as Lentinula edodes. This is an edible species used in medicine because of its beneficial anti-cancer, hypocholesterolemic, hypotensive, hypoglycemic and antioxidant effects. Due to the fact that the mycelium of L. edodes produces enzymes with oxidizing properties that can degrade xenobiotics. The aim of the work was verification if in vitro cultures of L. edodes can be used for bioremediation of non-steroidal, anti-inflammatory drug: piroxicam. For this purpose, the in vitro culture of L. edodes was derived and the mycelial cultures of this species enriched with piroxicam were analyzed. The biodegradation pathway of piroxicam by L. edodes mycelium was carried out by the UPLC/MS/MS method. The degradation process of piroxicam was found to affect primarily the linker between the thiazine and the piperidine ring, leading to its oxidation and cleavage. Additionally, oxidation of the benzothiazine moiety was observed, leading to hydroxylation and oxidation of the phenyl ring as well as oxidation of the thiazine ring leading to partial or complete removal of the sulfonamide moiety. It seems that the degradation process led finally to 2-hydroxybenozquinone, which may be further oxidized to inorganic compounds. What's more, concentration of piroxicam in in vitro cultures of L. edodes was not correlated with effectiveness of biodegradation of this compound - on each experimental series, the level of degradation was the same. The results confirm the possibility of using the investigated L. edodes mycelium for remediation of piroxicam.

Piroxicam is a non-steroidal anti-inflammatory drug belongs to BCS class II drugs having poor solubility and is associated with a number of undesirable side-effects on the stomach and kidneys in addition to gastric mucosal damage.

Low water solubility frequently compromises the therapeutic efficacy of drugs and other biologically active molecules. Here, we report on coacervate polysaccharide nanoparticles (CPNs) that can transport and release a model hydrophobic drug, piroxicam, to the cells in response to changes in temperature. The proposed, temperature-responsive drug delivery system is based on ionic derivatives of natural polysaccharides-curdlan and hydroxypropyl cellulose. Curdlan was modified with trimethylammonium groups, while the anionic derivative of hydroxypropyl cellulose was obtained by the introduction of styrenesulfonate groups. Thermally responsive nanoparticles of spherical shape and average hydrodynamic diameter in the range of 250-300 nm were spontaneously formed in water from the obtained ionic polysaccharides as a result of the coacervation process. Their morphology was visualized using SEM and AFM. The size and the surface charge of the obtained objects could be tailored by adjusting the polycation/polyanion ratio. Piroxicam (PIX) was effectively entrapped inside the nanoparticles. The release profile of the drug from the CPNs-PIX was found to be temperature-dependent in the range relevant for biomedical applications.

The objectives of this study are the synthesis of thermosensitive poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate), p(NiPAm-HPMet), hydrogels and the analysis of a drug-delivery system based on piroxicam, as a model drug, and synthesized hydrogels. A high pressure liquid chromatography method has been used in order to determine both qualitative and quantitative amounts of unreacted monomers and crosslinkers from polymerized hydrogels. Swelling kinetics and the order of a swelling process of the hydrogels have been analyzed at 10 and 40 °C. The copolymers' thermal properties have been monitored by the differential scanning calorimetry (DSC) method. DSC termograms have shown that melting occurs in two temperature intervals (142.36-150.72 °C and 153.14-156.49 °C). A matrix system with incorporated piroxicam has been analyzed by using FTIR and SEM methods. Structural analysis has demonstrated that intermolecular non-covalent interactions have been built between side-groups of copolymer and loaded piroxicam. Morphology of p(NiPAm-HPMet) after drug incorporation indicates the piroxicam presence into the copolymer pores. Kinetic parameters of the piroxicam release from hydrogels at 37 °C and pH 7.4 indicate that the fluid transport mechanism corresponds to Fickian diffusion. As a result, formulation of thermosensitive p(NiPAm-HPMet) hydrogels with incorporated piroxicam could be of interest for further testing as a drug carrier for modulated and prolonged release, especially for topical administration.

To investigate the antidepressant-like effect of piroxicam with a focus on serotonergic neurotransmission.

The purpose of this study was to investigate the effects of piroxicam co-administration with ethanolic stem-bark extract of Khaya senegalensis on biomarkers of oxidative stress and gastro-toxicity in Wistar rats.

Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 μm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration-time curve (AUC0-24 h) and maximum plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint.

Several biologically relevant phospholipids were assessed as potential carriers/additives for rapidly dissolving solid formulations of piroxicam (Biopharmaceutics Classification System Class II drug). On the basis of in vitro dissolution studies, dimyristoylphosphatidylglycerol (DMPG) was ranked as the first potent dissolution rate enhancer for the model drug. Subsequently, the solid dispersions of varying piroxicam/DMPG ratios were prepared and further investigated. Within the concentration range studied (6.4-16.7 wt %), the dissolution rate of piroxicam from the solid dispersions appeared to increase as a function of the carrier weight fraction, whereas the cumulative drug concentration was not significantly affected by piroxicam/DMPG ratio, presumably due to a unique phase behavior of the aqueous dispersions of this carrier phospholipid. Solid state analysis of DMPG-based formulations reveled that they are two-component systems, with a less thermodynamically stable form of piroxicam (Form II) being dispersed within the carrier. Finally, oral bioavailability of piroxicam from the DMPG-based formulations in rats was found to be superior to that of the control, as indicated by the bioavailability parameters, cmax and especially Tmax (53 µg/mL within 2 h vs. 39 µg/mL within 5.5 h, respectively). Hence, DMPG was regarded as the most promising carrier phospholipid for enhancing oral bioavailability of piroxicam and potentially other Class II drugs.

The aim of the study was to develop piroxicam-Aloe vera gel (PAG) formulation and make a pharmacodynamic evaluation of the formulation.

A suitable emulgel formulation of piroxicam was prepared and its percutaneous permeation was investigated using Wistar rat skin and diffusion cell technique. The concentrations of the drug in receptor phase of diffusion cells were measured using HPLC method. The effect of three types of penetration enhancers (Myrj 52, cineol and Transcutol P) with different concentrations on transdermal permeation of the drug was also evaluated. Flux, Kp and enhancement ratios (ERs) of piroxicam in the presence of enhancers was measured and compared with emulgel base alone and simple commercial gel. The results showed a significant enhancement in the flux from emulgel base compared to hydroalcoholic gel formulation (9.91 folds over simple gel). The highest enhancement ratio (ER=3.11) was observed for Myrj 52 at the concentration of 0.25%. Higher concentrations of Myrj 52did not show any enhancement in the drug flux due to micelle formation and solubilization of the drug by micelles. The increase in solubility, in turn, increases the saturated concentration and reduces the thermodynamic activity of the drug. Transcutol(®) P with concentrations higher than 0.25% w/w showed burst transportation of the drug through the skin. All concentrations of cineol and Transcutol did not show any enhancing effects over emulgel base alone (ER <1).

BACKGROUND NSAIDs are the most common agents used in dysmenorrhea treatment. They reduce menstrual pain by reducing uterine pressure and PGF2alpha levels in the menstrual fluid. The aim of this study was to compare the effects of piroxicam and diclofenac sodium as treatments for primary dysmenorrhea. MATERIAL AND METHODS The study was conducted using a randomized and double-blind method. Patients with Visual Analogue Scale (VAS) scores greater than 5 were accepted into the study. The patients who were suitable for inclusion were randomized into 2 groups and received either intramuscular piroxicam or diclofenac sodium. The patients' pain levels were measured at baseline and at 15, 30, 45, and 60 min. A VAS of 10 cm, a numeric scale, a verbal scale, and additional symptoms, as well as pain relapse after 24 hours and required analgesics, were recorded. RESULTS The study included 400 patients. Overall, 200 patients (50%) were in the proxicam group, and 200 patients were in the diclofenac sodium group. The average decrease on the VAS after piroxicam or diclofenac administration was measured as 7.9±1.8 cm and 7.9±1.7 cm (median ± standard deviation), respectively. The pain-reducing efficiency of all the treatments was compared using the Mann-Whitney U test (p=0.929). Rescue medication was needed for 25 patients in the proxicam group (p=0.014). Overall, 30 patients in the proxicam group and 41 patients in the proxicam group needed analgesics again in the 24-hour period after treatment (p=0.150). CONCLUSIONS At the end of our study, it was observed that there was no difference in the results of primary dysmenorrhea treatment with 20 mg piroxicam or 75 mg diclofenac sodium.

No abstract available

Peritoneal adhesions are fibrous bands of tissues formed between organs that are normally separated and/or between organs and the internal body wall after peritoneal injury. Antiinflammatory agents were used to reduce the initial inflammatory response to tissue injury and, hence, the subsequent formation of adhesion. The aim of this study was to investigate the effect of intraperitoneal instillation of piroxicam on intraperitoneal adhesions.

Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.

Piroxicam has been shown to prevent azoxymethane (AOM)-induced aberrant crypt foci and colon cancer in rats. In this communication we evaluate whether piroxicam can also cause regression of precancerous lesions identified as aberrant crypt foci, thus preventing the occurrence of cancer. Male Fischer-344 rats were administered 0.125 g/kg piroxicam in their diet starting either 1 week prior to or 12 weeks after a single subcutaneous injection of AOM (30 mg/kg body wt). The yield of aberrant crypt foci and of colon adenomas and adenocarcinomas was determined at 5, 12, 27 and 37 weeks after administering the AOM respectively. When piroxicam was administered starting 1 week prior to AOM the yield of aberrant crypt foci at the three initial time points was reduced. When the administration of piroxicam was delayed until 12 weeks after AOM the yield of aberrant crypt foci was reduced from 53.8 +/- 8.1 foci/colon at 12 weeks to 11.1 +/- 2.0 at 27 weeks. At 37 weeks after administering AOM the yield of colon tumors was 0.59 +/- 0.11 tumors/animal, while in rats administered piroxicam beginning either 1 week prior to or 12 weeks after AOM the yield was similarly reduced to 0.14 +/- 0.07 and 0.17 +/- 0.07 tumors/animal respectively. Thus piroxicam was demonstrated not only to prevent, but also to cause regression of aberrant crypt foci, both of which were associated with the prevention of colon tumors.

Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.

Piroxicam exhibits low oral bioavailability, due to its meager solubility in water. The intent of this study was to ameliorate the bioavailability of the drug by employing a solubility-enhancing encapsulation technique.

Simple and rapid capillary zone electrophoretic method was developed and validated in this study for the determination of piroxicam in tablets. The separation of piroxicam was conducted in a fused-silica capillary by using 10 mM borate buffer (pH 9.0) containing 10% (v/v) methanol as background electrolyte. The optimum conditions determined were 25 kV for separation voltage and 1 s for injection time. Analysis was carried out with UV detection at 204 nm. Naproxen sodium was used as an internal standard. The method was linear over the range of 0.23-28.79 µg/mL. The accuracy and precision were found to be satisfied within the acceptable limits (<2%). The LOD and LOQ were found to be 0.07 and 0.19 µg/mL, respectively. The method described here was applied to tablet dosage forms and the content of a tablet was found in the limits of USP-24 suggestions. To compare the results of capillary electrophoretic method, UV spectrophotometric method was developed and the difference between two methods was found to be insignificant. The capillary zone electrophoretic method developed in this study is rapid, simple, and suitable for routine analysis of piroxicam in pharmaceutical tablets.

This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin E2 in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.