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International Journal of Nanomedicine 2020Meloxicam (MX) is a potent hydrophobic non-steroidal anti-inflammatory drug used to reduce inflammation and pain. However, its oral dosage form can cause many adverse...
BACKGROUND AND AIM
Meloxicam (MX) is a potent hydrophobic non-steroidal anti-inflammatory drug used to reduce inflammation and pain. However, its oral dosage form can cause many adverse gastrointestinal effects. In the present study, a poloxamer P407 based hydrogel system containing transfersomes or flavosomes has been prepared as a potential therapeutic vehicle for the topical delivery of MX.
METHODS
In this study, MX was encapsulated in conventional liposomes, transfersomes, and flavosomes. The obtained liposomal vesicles were characterized in terms of size, drug entrapment efficiency, zeta potential, and stability. These MX-loaded liposomal formulations were further incorporated into a poloxamer P407 gel and evaluated using rheological properties, a stability study and an ex vivo permeation study through human cadaver skin by both HPLC analysis and confocal laser scanning microscopy (CLSM).
RESULTS
The developed deformable liposomes exhibited homogeneous vesicle sizes less than 120 nm with a higher entrapment efficiency as compared to conventional liposomes. The deformable liposomal gel formulations showed improved permeability compared to a conventional liposomal gel and a liposome-free gel. The enhancement effect was also clearly visible by CLSM.
CONCLUSION
These deformable liposomal hydrogel formulations can be a promising alternative to conventional oral delivery of MX by topical administration. Notably, flavosome-loaded gel formulations displayed the highest permeability through the deeper layers of the skin and shortened lag time, indicating a potential faster on-site pain relief and anti-inflammatory effect.
Topics: Administration, Cutaneous; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Hydrogels; Hydrophobic and Hydrophilic Interactions; Liposomes; Male; Mechanical Phenomena; Meloxicam; Particle Size; Permeability; Skin; Skin Absorption; Swine
PubMed: 33262590
DOI: 10.2147/IJN.S274954 -
Oncology Letters Aug 2017Cyclooxygenase (COX)-2 expression is positively correlated with malignant features in canine mammary carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit...
Cyclooxygenase (COX)-2 expression is positively correlated with malignant features in canine mammary carcinomas. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX activity and may therefore possess anticancer effects. Meloxicam is an NSAID that is widely used in human and veterinary medicine. High concentrations of meloxicam have been reported to be antitumorigenic ; however, the effect of meloxicam at concentrations that are equivalent to those that can be obtained remains unknown. In the current study, the effects of low-dose meloxicam (0.25 µg/ml) on CF41.Mg canine mammary carcinoma cells were evaluated. The effects on cell proliferation, apoptosis, cell migration and invasion, in addition to the expression of different molecules associated with tumor invasiveness were analyzed. No effect on cell viability and apoptosis were observed. However, cell migration and invasion were significantly reduced following treatment with meloxicam. MMP-2 expression and activity were similarly reduced, explaining the impaired cell invasion. In addition, β-catenin expression was downregulated, while its phosphorylation increased. These results indicate that 0.25 µg/ml meloxicam reduces cell migration and invasion, in part through modulating MMP-2 and β-catenin expression. Additional studies are required to elucidate the mechanism associated with the anti-invasive effect of meloxicam on CF41.Mg cells. The results of the present study suggest that meloxicam has a potential adjunctive therapeutic application, which could be useful in controlling the invasion and metastasis of canine mammary carcinomas.
PubMed: 28781660
DOI: 10.3892/ol.2017.6400 -
Scientific Reports Mar 2019Non-steroidal anti-inflammatories (NSAIDs), such as meloxicam, are the mainstay for treating painful and inflammatory conditions in animals and humans; however, the...
Non-steroidal anti-inflammatories (NSAIDs), such as meloxicam, are the mainstay for treating painful and inflammatory conditions in animals and humans; however, the repeated administration of NSAIDs can cause adverse effects, limiting the long-term administration of these drugs to some patients. The primary aim of this study was to determine the effects of repeated meloxicam administration on the feline plasma and urine lipidome. Cats (n = 12) were treated subcutaneously with either saline solution or 0.3 mg/kg body weight of meloxicam daily for up to 31 days. Plasma and urine lipidome were determined by LC-MS before the first treatment and at 4, 9 and 13 and 17 days after the first administration of meloxicam. The repeated administration of meloxicam altered the feline plasma and urine lipidome as demonstrated by multivariate statistical analysis. The intensities of 94 out of 195 plasma lipids were altered by the repeated administration of meloxicam to cats (p < 0.05). Furthermore, we identified 12 lipids in plasma and 10 lipids in urine that could serve as biomarker candidates for discriminating animals receiving NSAIDs from healthy controls. Expanding our understanding about the effects of NSAIDs in the body could lead to the discovery of mechanism(s) associated with intolerance to NSAIDs.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers, Pharmacological; Cats; Chromatography, High Pressure Liquid; Female; Humans; Lipid Metabolism; Lipidomics; Lipids; Male; Mass Spectrometry; Meloxicam; Time Factors
PubMed: 30867479
DOI: 10.1038/s41598-019-40686-4 -
Molecules (Basel, Switzerland) May 2012The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and... (Review)
Review
The presented review summarizes experimental data obtained with a mouse model when investigating the relationship between inhibition of prostaglandin production and hematopoiesis. While prostaglandin E2 acts in a negative feedback control of myelopoiesis, inhibition of cyclooxygenases, responsible for its production, shifts the feedback to positive control. Based on these relationships, agents inhibiting cyclo-oxygenases, known as non-steroidal anti-inflammatory drugs (NSAIDs), can activate hematopoiesis and be protective or curative under myelosuppressive states. The effectiveness of therapeutic use of NSAIDs in these situations is expressive especially under the selective inhibition of cyclooxygenase-2 (COX-2), when undesirable side effects of cyclooxygenase-1 inhibition, like gastrointestinal damage, are absent. The effects of the clinically approved selective COX-2 inhibitor, meloxicam, were investigated and demonstrated significant hematopoiesis-stimulating and survival-enhancing actions of this drug in sublethally or lethally γ-irradiated mice. These effects were connected with the ability of meloxicam to increase serum levels of the granulocyte colony-stimulating factor. It can be inferred from these findings that selective COX-2 inhibitors might find their use in the treatment of myelosuppressions of various etiologies.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprostone; Feedback, Physiological; Gamma Rays; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Humans; Meloxicam; Mice; Myelopoiesis; Thiazines; Thiazoles
PubMed: 22576231
DOI: 10.3390/molecules17055615 -
Poultry Science Aug 2023Birds use their legs and wings when transitioning from aerial to ground locomotion during landing. To improve our understanding of the effects of footpad dermatitis...
Birds use their legs and wings when transitioning from aerial to ground locomotion during landing. To improve our understanding of the effects of footpad dermatitis (FPD) and keel bone fracture (KBF) upon landing biomechanics in laying hens, we measured ground-reaction forces generated by hens (n = 37) as they landed on force plates (Bertec Corporation, Columbus, OH) from a 30 cm drop or 170 cm jump in a single-blinded placebo-controlled trial using a cross-over design where birds received an anti-inflammatory (meloxicam, 5 mg/kg body mass) or placebo treatment beforehand. We used generalized linear mixed models to test for effects of health status, treatment and their interaction on landing velocity (m/s), maximum resultant force (N), and impulse (force integrated with respect to time [N s]). Birds with FPD and KBF tended to show divergent alterations to their landing biomechanics when landing from a 30 cm drop, with a higher landing velocity and maximum force in KBF compared to FPD birds, potentially indicative of efforts to either reduce the use of their wings or impacts on inflamed footpads. In contrast, at 170 cm jumps fewer differences between birds of different health statuses were observed likely due to laying hens being poor flyers already at their maximum power output. Our results indicate that orthopedic injuries, apart from being welfare issues on their own, may have subtle influences on bird mobility through altered landing biomechanics that should be considered.
Topics: Animals; Female; Biomechanical Phenomena; Bone and Bones; Chickens; Fractures, Bone; Meloxicam; Cross-Over Studies
PubMed: 37307632
DOI: 10.1016/j.psj.2023.102794 -
JAMA Internal Medicine Sep 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects.
OBJECTIVE
To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis.
DESIGN, SETTING, AND PARTICIPANTS
The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis.
INTERVENTIONS
Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2).
MAIN OUTCOMES AND MEASURES
The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks.
RESULTS
A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks.
CONCLUSIONS AND RELEVANCE
Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01799213.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cognitive Behavioral Therapy; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Telemedicine; Treatment Outcome
PubMed: 32702101
DOI: 10.1001/jamainternmed.2020.2821 -
Drug Delivery Dec 2022Combination therapy combining two drugs in one modified drug delivery system is used to achieve synergistic analgesic effect, and bring effective control of pain...
Combination therapy combining two drugs in one modified drug delivery system is used to achieve synergistic analgesic effect, and bring effective control of pain management, especially postoperative pain management. In the present study, a combination of drug delivery technologies was utilized. Transcriptional transactivator (TAT) peptide modified, transdermal nanocarriers were designed to co-deliver ropivacaine (RVC) and meloxicam (MLX) and anticipated to achieve longer analgesic effect and lower side effect. TAT modified nanostructured lipid carriers (TAT-NLCs) were used to co-deliver RVC and MLX. RVC and MLX co-loaded TAT-NLCs (TAT-NLCs-RVC/MLX) were evaluated through skin permeation and treatment studies. NLCs-RVC/MLX showed uniform and spherical morphology, with a size of 133.4 ± 4.6 nm and a zeta potential of 20.6 ± 1.8 mV. The results illustrated the anesthetic pain relief ability of the present constructed system was significantly improved by the TAT modification through the enhanced skin permeation efficiency and the co-delivery of MLX along with RVC that improved pain management by reducing inflammation at the injured area. This study provides an efficient and facile method for preparing TAT-NLCs-RVC/MLX as a promising system to achieve synergistic analgesic effect.
Topics: Analgesics; Animals; Cell Survival; Chemistry, Pharmaceutical; Drug Carriers; Drug Combinations; Drug Liberation; Drug Synergism; Lipids; Meloxicam; Nanoparticle Drug Delivery System; Particle Size; Rats; Rats, Sprague-Dawley; Ropivacaine; Skin Absorption; Surface Properties; Trans-Activators
PubMed: 35014916
DOI: 10.1080/10717544.2021.2023695 -
American Journal of Veterinary Research Mar 2010To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy...
OBJECTIVE
To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.
ANIMALS
10 hound-crossbred dogs.
PROCEDURES
Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B(2) and 6-keto prostaglandin (PG)F(1alpha) were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation.
RESULTS
Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50microM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB(2) and 6-keto PGF(1alpha) concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval.
CONCLUSIONS AND CLINICAL RELEVANCE
Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB(2) and 6-keto PGF(1alpha) concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2-selective inhibitors on hemostasis should be performed.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Blood Coagulation; Blood Platelets; Carbazoles; Dogs; Female; Male; Meloxicam; Ovariectomy; Platelet Aggregation; Prostaglandins; Sulfonamides; Thiazines; Thiazoles
PubMed: 20187838
DOI: 10.2460/ajvr.71.3.349 -
British Journal of Pharmacology Dec 20001. Since nonsteroidal anti-inflammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in...
1. Since nonsteroidal anti-inflammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. 2. Explants were sampled from the medial femoral condyle and were classified by use of the Mankin's histological-histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3. Cartilage explants were pulsed with [-3H]-glucosamine and chased in the absence or in the presence of 0.3 - 3 microg ml(-1) of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaffected by diclofenac. In contrast, and in a dose-dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced significantly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from cartilage explants. 5. The data obtained in short-term in vitro cultures indicate that, at the concentrations found in synovial fluid, aceclofenac and meloxicam may exert a favourable effect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Culture Techniques; Diclofenac; Dose-Response Relationship, Drug; Extracellular Matrix; Humans; Hyaluronic Acid; Meloxicam; Osteoarthritis; Proteoglycans; Thiazines; Thiazoles
PubMed: 11090115
DOI: 10.1038/sj.bjp.0703710 -
American Journal of Veterinary Research Apr 2013To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses.
OBJECTIVE
To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses.
ANIMALS
6 healthy rabbits.
PROCEDURES
A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed.
RESULTS
The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE
Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Drug Administration Schedule; Half-Life; Meloxicam; Rabbits; Thiazines; Thiazoles
PubMed: 23531074
DOI: 10.2460/ajvr.74.4.636