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Colloids and Surfaces. B, Biointerfaces Aug 2023Meloxicam (MLX) is prescribed for the management of pain and inflammation allied with osteoarthritis (OA). However, MLX causes intestinal damage in long term...
BACKGROUND AND OBJECTIVE
Meloxicam (MLX) is prescribed for the management of pain and inflammation allied with osteoarthritis (OA). However, MLX causes intestinal damage in long term administration. Hence, meloxicam loaded emulgel (MLX-emulgel) was optimized, formulated and examined under stringent parameters in monosodium-iodoacetate (MIA) induced knee OA in Wistar rats.
METHODS AND RESULTS
Nanoemulsion of MLX was fabricated by ultrasonication and microfluidization method with a droplet size of 66.81 ± 5.31-nm and zeta potential of -24.6 ± 0.72-mV. Further, MLX nanoemulsion was optimized with centrifugation, heating-cooling cycles and transmittance parameters in addition to scale-up feasibility with microfluidizer. Post optimization, MLX-nanoemulsion was tailored as emulgel with Carbopol Ultrez 10 NF and assessed for pH, rheology, textural properties, assay and stability features. The in-vitro release study revealed the Korsmeyer-Peppas release kinetics and ex-vivo skin permeation was improved by 6.71-folds. The skin distribution of MLX-emulgel evinced the transfollicular mode of permeation. In-vivo study indicated the protective action of MLX-emulegl expressed in terms of inflammatory cyctokines level, X-ray analysis of knee joints of rats, histopathology and OARSI (Osteoarthritis Research Society International) scoring. MLX-emulgel treated group displayed lower (P < 0.001) level of COX-2 intensity as compared to positive control group. However, it was comparable (P > 0.05) to the normal control group, MLX oral dispersion, i.v. solution and etoricoxib gel groups. MLX-emulgel showcased an alternative to the long term usage of analgesics for relieving the symptoms of knee OA.
CONCLUSION
MLX-emulgel may be a potential candidate for translating in to a clinically viable dosage form in the management of knee OA.
Topics: Rats; Animals; Meloxicam; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis, Knee; Rats, Wistar; Skin
PubMed: 37348266
DOI: 10.1016/j.colsurfb.2023.113399 -
Drug and Chemical Toxicology Mar 2022Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in...
Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects.
Topics: Animals; Comet Assay; DNA Damage; Heart; Liver; Male; Meloxicam; Mice; Micronucleus Tests
PubMed: 32552192
DOI: 10.1080/01480545.2020.1778018 -
Journal of Animal Science Jan 2023Each suckling pig should receive ≥200 g of colostrum within the first 24 h of life, but with increased litter size this is now difficult to achieve. The aim of this...
Each suckling pig should receive ≥200 g of colostrum within the first 24 h of life, but with increased litter size this is now difficult to achieve. The aim of this study was to assess the effect of split-suckling and postpartum meloxicam provision to sows as a means of ensuring adequate colostrum intake, on growth and health in pigs pre- and postweaning. One hundred and four sows (Large White × Landrace) and their litters, averaging 16.3 piglets born alive, were assigned to one of four treatments in a two-by-two factorial arrangement. Factors were provision of meloxicam (yes/no; Mel/N-Mel) and split-suckling (yes/no; Split/N-Split). Meloxicam was administered intramuscularly at 0.4 mg/kg body weight to sows on release of the placenta (~2 h postpartum). Split-suckling commenced 4 h after birth of the first piglet, with the six heaviest piglets removed from the sow for 1 h to allow the lightest piglets to suckle. This was repeated after 1.5 h. Pigs were weighed at birth and at days 1, 6, 14, and 27 after birth and at days 6, 14, 21, 28, 47, and 129 postweaning. Carcass data were collected at slaughter. Medication usage was recorded from birth to slaughter. There was a split-suckling by meloxicam interaction effect at days 1 to 6 (P < 0.001) and days 6 to 14 (P < 0.001) after birth. Meloxicam administration had no effect on average daily gain (ADG) when split-suckling was applied; however, when split-suckling was not applied, postpartum meloxicam administration increased ADG. There was a meloxicam × split-suckling interaction for ADG from weaning to day 6 postweaning (P = 0.03). Meloxicam increased ADG when split-suckling was applied but not in its absence. Carcass weight was increased by meloxicam (P = 0.01) but was not affected by split-suckling (P > 0.05). Meloxicam use in sows reduced the number of clinical cases of disease (P = 0.04) in suckling pigs which tended to reduce the volume of antibiotics (P = 0.08) and anti-inflammatories (P = 0.08) administered. Split-suckling had no effect on medication usage in sows and piglets during lactation but increased their use from weaning to slaughter. In conclusion, postpartum administration of meloxicam to sows is an easily implemented strategy. It reduced clinical cases of disease, increased ADG in pigs during the first two weeks of life and early postweaning and increased carcass weight at slaughter. However, no split-suckling benefit was observed.
Topics: Female; Pregnancy; Animals; Swine; Meloxicam; Incidence; Postpartum Period; Parturition; Lactation; Weight Gain
PubMed: 37591793
DOI: 10.1093/jas/skad275 -
Brazilian Dental Journal 2017This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone...
This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Mandible; Meloxicam; Radiation-Protective Agents; Rats; Thiazines; Thiazoles; X-Ray Microtomography
PubMed: 28492757
DOI: 10.1590/0103-6440201701271 -
Journal of Controlled Release :... Jan 2023Poly(lactide-co-glycolide) (PLGA) polymers have been widely used for drug delivery due to their biodegradability and biocompatibility. One of the objectives of...
Poly(lactide-co-glycolide) (PLGA) polymers have been widely used for drug delivery due to their biodegradability and biocompatibility. One of the objectives of encapsulating a drug in PLGA microparticles (MPs) is to achieve an extended supply of the drug through sustained release, which can range from weeks to months. Focusing on the applications needing a relatively short-term delivery, we investigated formulation strategies to achieve a drug release from PLGA MPs for two weeks, using meloxicam as a model compound. PLGA MPs produced by the traditional oil/water (O/W) single emulsion method showed only an initial burst release with minimal increase in later-phase drug release. Alternatively, encapsulating meloxicam as solid helped reduce the initial burst release. The inclusion of magnesium hydroxide [Mg(OH)] enhanced later-phase drug release by neutralizing the developing acidity that limited the drug dissolution. The variation of solid meloxicam and Mg(OH) quantities allowed for flexible control of meloxicam release, yielding MPs with distinct in vitro release kinetics. When subcutaneously injected into rats, the MPs with relatively slow in vitro drug release kinetics showed in vivo drug absorption profiles consistent with in vitro trend. However, the MPs that rapidly released meloxicam showed an attenuated in vivo absorption, suggesting premature precipitation of fast-released meloxicam. In summary, this study demonstrated the feasibility of controlling drug release from the PLGA MPs over weeks based on the physical state of the encapsulated drug and the inclusion of Mg(OH) to neutralize the microenvironmental pH of the MPs.
Topics: Rats; Animals; Polylactic Acid-Polyglycolic Acid Copolymer; Meloxicam; Polyglactin 910; Drug Delivery Systems; Drug Liberation; Particle Size; Microspheres
PubMed: 36521690
DOI: 10.1016/j.jconrel.2022.12.019 -
Journal of Veterinary Emergency and... May 2022To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration.
OBJECTIVE
To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration.
SERIES SUMMARY
Three cases were treated with meloxicam for variable nonspecific signs including lethargy and pyrexia. Hemorrhagic diarrhea developed following meloxicam administration in 2 cases. Gastrointestinal perforation was suspected on diagnostic imaging leading to exploratory celiotomy in all 3 cases. Partial colectomy was performed in 2 cases and suture repair with serosal patching in 1 followed by broad spectrum antimicrobials. All 3 dogs recovered from surgery well. One dog that had undergone perineal herniorrhaphy and received meloxicam perioperatively collapsed and died 7 days postsurgery. Postmortem examination revealed ulceration and perforation of the ascending colon with resultant generalized septic peritonitis. Histopathologic findings in all cases showed full thickness infiltration of the colonic wall with inflammatory cells along with ulceration and perforation. Thrombosis of vessels underlying the ulcerated areas was also noted.
NEW OR UNIQUE INFORMATION PROVIDED
This report suggests that colonic perforation may be a complication of nonsteroidal anti-inflammatory drug use in some cases. To the authors' knowledge, this has not previously been described in dogs. Colonic perforation associated with NSAIDs administration may be more commonly identified in dogs with concurrent morbidities. Caution may be warranted when using NSAIDs in dogs with colonic pathology or possible risk factors to develop such pathology. Prompt diagnosis and treatment is essential for a positive outcome.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Intestinal Perforation; Meloxicam; Peritonitis
PubMed: 35043544
DOI: 10.1111/vec.13170 -
Journal of the American Association For... Jan 2023Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to...
Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.
Topics: Female; Mice; Animals; Meloxicam; Pain Management; Anti-Inflammatory Agents, Non-Steroidal; Pain; Analgesia; Analgesics; Thiazines; Pain, Postoperative
PubMed: 36755203
DOI: 10.30802/AALAS-JAALAS-22-000064 -
Materials Science & Engineering. C,... Dec 2020The in situ forming system has attracted attention for periodontitis treatment owing to its sustainable drug release localisation at a periodontal pocket. Given its low...
The in situ forming system has attracted attention for periodontitis treatment owing to its sustainable drug release localisation at a periodontal pocket. Given its low aqueous solubility, beta-cyclodextrin (β-CD) may serve as a matrix former of solvent exchange-induced in situ forming gel (ISG) and microparticle (ISM). Meloxicam (Mex)-loaded-β-CD ISG and ISM were prepared using β-CD in dimethyl sulphoxide (ISG) as the internal phase and camellia oil comprising 5% glyceryl monostearate as the external phase (ISM). Mex-loaded β-CD systems comprising 40% β-CD were easily injected via a 24-gauge needle. During solvent exchange with phosphate buffer saline (pH 6.8), the highly concentrated β-CD ISG promoted the phase inversion of β-CD aggregates into matrix-like. Upon exposure to aqueous phase, the ISM system comprising 40% β-CD transformed into microparticles and extended the drug release to 7 days with minimised initial burst release following Fickian diffusion. Moreover, the potential degradability was evident from the high weight loss. High maximum deformation force with high viscous character initiated the slow diffusion rate of the solvent from the ISM system. Therefore, 40% β-CD ISM is a potential local Mex-controlled release system of anti-inflammatory drug for periodontitis treatment.
Topics: Drug Delivery Systems; Humans; Meloxicam; Periodontal Pocket; Solubility; Solvents; beta-Cyclodextrins
PubMed: 32919639
DOI: 10.1016/j.msec.2020.111275 -
Veterinary and Comparative Oncology Dec 2021This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose...
This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.
Topics: Adjuvants, Immunologic; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cat Diseases; Cats; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Mammary Neoplasms, Animal; Mastectomy; Meloxicam; Retrospective Studies; Survival Rate
PubMed: 33140523
DOI: 10.1111/vco.12660 -
Veterinary Surgery : VS May 2019To compare meloxicam and robenacoxib for short-term postoperative pain management after combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy.
OBJECTIVE
To compare meloxicam and robenacoxib for short-term postoperative pain management after combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy.
STUDY DESIGN
Double-blind, prospective, randomised clinical trial.
ANIMALS
Twenty-six client-owned female dogs.
METHODS
Dogs undergoing combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy were randomly divided into 2 groups. Before induction of anesthesia, 13 dogs received meloxicam (0.2 mg/kg subcutaneously), and 13 dogs received robenacoxib (2 mg/kg subcutaneously). Pain was scored with the Glasgow Composite Pain Scale (short form) before surgery and at 1, 6, 12, 18, and 24 hours after extubation. Rescue analgesia (tramadol, 3 mg/kg) was provided to dogs with a Glasgow pain score (GPS) ≥5. Glasgow pain scores were analyzed by ANOVA with treatment, age, and surgical time as fixed factors.
RESULTS
Glasgow pain scores were higher at 24 hours postsurgery in dogs treated with robenacoxib (2.18 ± 0.29) compared with those treated with meloxicam (0.68 ± 0.41, P = .04). Two dogs treated with meloxicam and 7 dogs treated with robenacoxib required rescue analgesia. Regardless of the treatment, the overall GPS was lower at 18 and 24 hours postsurgery when the surgical time was >40 minutes compared with surgical times ≤40 minutes, but surgical site inflammation was likely a confounding factor in this finding. Glasgow pain score was not affected by patient age.
CONCLUSION
Meloxicam was more effective than robenacoxib at controlling pain in the population of dogs reported here.
CLINICAL SIGNIFICANCE
Preoperative administration of meloxicam effectively controls pain for 24 hours after combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy, but rescue analgesia may be required.
Topics: Analgesia; Anesthesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diphenylamine; Dogs; Double-Blind Method; Female; Gastropexy; Laparoscopy; Meloxicam; Ovariectomy; Pain Management; Pain Measurement; Pain, Postoperative; Phenylacetates; Prospective Studies; Random Allocation
PubMed: 30637777
DOI: 10.1111/vsu.13156