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Scientific Reports Jan 2024This study presents two spectrophotometric methods; a novel dual wavelength-derivative spectrophotometry and multivariate curve resolution-alternating least squares...
This study presents two spectrophotometric methods; a novel dual wavelength-derivative spectrophotometry and multivariate curve resolution-alternating least squares (MCR-ALS) for the simultaneous determination of a fixed dose combination of bupivacaine (BUP) and meloxicam (MEL) in a ratio of 30:1. The extended UV spectrum of MEL enables its direct determination at λ 360 nm with no interference from BUP. The determination of BUP was unfeasible directly because the UV spectra of both drugs are moderately overlapped over the wavelength range of 250-450 nm, thus new chemometric based spectrophotometric methods should be developed for its determination. Dual wavelength-derivative method was employed based on using first derivative spectra. The selected dual wavelengths for determination BUP were 274.6 nm and 374.6 nm where the dA/dλ amplitudes differences for MET are equal to zero. MCR-ALS is advanced chemometric tool that enables analysis of multicomponent samples in complex matrices with high resolution based on the decomposition of signal/spectral data into the pure spectra and corresponding concentration profile. The figures of merits for MCR model show that there is a good agreement between the actual and predicted concentrations for MEL and BUP. The methods were validated and statistically compared with a reported HPLC method.
Topics: Meloxicam; Chemometrics; Bupivacaine; Chromatography, High Pressure Liquid; Spectrophotometry
PubMed: 38253707
DOI: 10.1038/s41598-024-51885-z -
Gels (Basel, Switzerland) Jan 2024Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless,... (Review)
Review
Topical and transdermal drug delivery are advantageous administration routes, especially when treating diseases and conditions with a skin etiology. Nevertheless, conventional dosage forms often lead to low therapeutic efficacy, safety issues, and patient noncompliance. To tackle these issues, novel topical and transdermal platforms involving nanotechnology have been developed. This review focuses on the latest advances regarding the development of nanoemulgels for skin application, encapsulating a wide variety of molecules, including already marketed drugs (miconazole, ketoconazole, fusidic acid, imiquimod, meloxicam), repurposed marketed drugs (atorvastatin, omeprazole, leflunomide), natural-derived compounds (eucalyptol, naringenin, thymoquinone, curcumin, chrysin, brucine, capsaicin), and other synthetic molecules (ebselen, tocotrienols, retinyl palmitate), for wound healing, skin and skin appendage infections, skin inflammatory diseases, skin cancer, neuropathy, or anti-aging purposes. Developed formulations revealed adequate droplet size, PDI, viscosity, spreadability, pH, stability, drug release, and drug permeation and/or retention capacity, having more advantageous characteristics than current marketed formulations. In vitro and/or in vivo studies established the safety and efficacy of the developed formulations, confirming their therapeutic potential, and making them promising platforms for the replacement of current therapies, or as possible adjuvant treatments, which might someday effectively reach the market to help fight highly incident skin or systemic diseases and conditions.
PubMed: 38247768
DOI: 10.3390/gels10010045 -
PloS One 2024Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research...
Usage and reporting of analgesia in animal models of spinal cord injury (SCI) have been sparse and requires proper attention. The majority of experimental SCI research uses rats as an animal model. This study aimed to probe into the effects of some commonly used regimens with NSAIDs and opioids on well-being of the rats as well as on the functional outcome of the model. This eight-week study used forty-two female Wistar rats (Crl: WI), randomly and equally divided into 6 treatment groups, viz. I) tramadol (5mg/kg) and buprenorphine (0.05mg/kg); II) carprofen (5mg/kg) and buprenorphine (0.05mg/kg); III) carprofen (5mg/kg); IV) meloxicam (1mg/kg) and buprenorphine (0.05mg/kg); V) meloxicam (1mg/kg); and VI) no analgesia (0.5 ml sterile saline). Buprenorphine was administered twice daily whereas other treatments were given once daily for five days post-operatively. Injections were given subcutaneously. All animals underwent dental burr-assisted laminectomy at the T10-T11 vertebra level. A custom-built calibrated spring-loaded 200 kilodynes force deliverer was used to induce severe SCI. Weekly body weight scores, Rat Grimace Scale (RGS), and dark-phase home cage activity were used as markers for well-being. Weekly Basso Beattie and Bresnahan (BBB) scores served as markers for functionality together with Novel Object Recognition test (NOR) at week 8 and terminal histopathology using area of vacuolisation and live neuronal count from the ventral horns of spinal cord. It was concluded that the usage of analgesia improved animal wellbeing while having no effects on the functional aspects of the animal model in comparison to the animals that received no analgesics.
Topics: Rats; Female; Animals; Laminectomy; Meloxicam; Rats, Wistar; Disease Models, Animal; Spinal Cord Injuries; Analgesics; Spinal Cord; Buprenorphine
PubMed: 38227583
DOI: 10.1371/journal.pone.0294720 -
Nanomaterials (Basel, Switzerland) Jan 2024Poorly water-soluble drugs represent a challenge for the pharmaceutical industry because it is necessary to find properly tuned and efficient systems for their release....
Poorly water-soluble drugs represent a challenge for the pharmaceutical industry because it is necessary to find properly tuned and efficient systems for their release. In this framework, organic-inorganic hybrid systems could represent a promising strategy. A largely diffused inorganic host is hydroxyapatite (HAP, Ca(PO)(OH)), which is easily synthesized with different external forms and can adsorb different kinds of molecules, thereby allowing rapid drug release. Hybrid nanocomposites of HAP nanorods, obtained through hydrothermal synthesis, were prepared with two model pharmaceutical molecules characterized by low and pH-dependent solubility: meloxicam, a non-steroidal anti-inflammatory drug, and bumetanide, a diuretic drug. Both hybrids were physically and chemically characterized through the combined use of X-ray powder diffraction, scanning electron microscopy with energy-dispersive spectroscopy, differential scanning calorimetry, and infrared spectroscopy measurements. Then, their dissolution profiles and hydrophilicity (contact angles) in different media as well as their solubility were determined and compared to the pure drugs. This hybrid system seems particularly suitable as a drug carrier for bumetanide, as it shows higher drug loading and good dissolution profiles, while is less suitable for meloxicam, an acid molecule.
PubMed: 38202568
DOI: 10.3390/nano14010113 -
Animals : An Open Access Journal From... Dec 2023Pain assessment is of paramount importance for properly managing dogs with osteoarthritis (OA) pain. The aim of the present study was to develop and psychometrically...
Pain assessment is of paramount importance for properly managing dogs with osteoarthritis (OA) pain. The aim of the present study was to develop and psychometrically validate the Italian version of the Helsinki Chronic Pain Index (I-HCPI). Owners of OA painful ( = 87) and healthy dogs ( = 40) were administered the I-HCPI once or twice after an eight-week meloxicam treatment. Sixty-nine owners of healthy and OA dogs also completed the Italian version of the Canine Brief Pain Inventory (I-CBPI). Pain on palpation on a 0-4 scale was assessed on all recruited dogs. Construct validity was tested both with hypothesis testing and principal component analysis, confirming the I-HCPI accurately measured chronic pain. Good convergent and criterion validity were shown through correlations with I-CBPI subscores and distribution among pain on palpation scores ( < 0.0001). The significant difference between the pre- and post-treatment I-HCPI scores ( < 0.0001) and Cohen's effect size (2.27) indicated excellent responsiveness. The I-HCPI was shown to be reliable through communalities (range 0.47-0.90) and Cronbach α (≥0.95). Discriminative ability and cut-off point, as tested through Receiver Operating Characteristic analysis, showed excellent diagnostic accuracy with a threshold value of 11 (specificity 0.98 and sensitivity 0.94). The I-HCPI was confirmed to be a valid, sensitive, reliable, and accurate tool to discriminate between dogs with and without pain.
PubMed: 38200814
DOI: 10.3390/ani14010083 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent...
Among the biological targets extensively investigated to improve inflammation and chronic inflammatory conditions, cyclooxygenase enzymes (COXs) occupy a prominent position. The inhibition of these enzymes, essential for mitigating inflammatory processes, is chiefly achieved through Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). In this work, we introduce a novel method-based on computational molecular docking-that could aid in the structure-based design of new compounds or the description of the anti-inflammatory activity of already-tested compounds. For this, we used eight crystal complexes (four COX-1 and COX-2 each), and each pair had a specific NSAID: Celecoxib, Meloxicam, Ibuprofen, and Indomethacin. This selection was based on the ligand selectivity towards COX-1 or COX-2 and their binding mode. An interaction profile of each NSAID was compiled to detect the residues that are key for their binding mode, highlighting the interaction made by the Me group. Furthermore, we rigorously validated our models based on structural accuracy (RMSD < 1) and (R > 70) using eight NSAIDs and thirteen compounds with IC values for each enzyme. Therefore, this model can be used for the binding mode prediction of small and structurally rigid compounds that work as COX inhibitors or the prediction of new compounds that are designed by means of a structure-based approach.
PubMed: 38139814
DOI: 10.3390/ph16121688 -
Marine Drugs Nov 2023Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel...
Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.
Topics: Animals; Sea Anemones; Meloxicam; Disease Models, Animal; Osteoarthritis; Inflammation; Pain; Anti-Inflammatory Agents; Analgesics; Peptides; Iodoacetic Acid
PubMed: 38132938
DOI: 10.3390/md21120617 -
Cureus Nov 2023Pruritus, colloquially known as itch, is a common clinical symptom seen in a variety of dermatological conditions and systemic disorders. Pruritus can broadly be...
Pruritus, colloquially known as itch, is a common clinical symptom seen in a variety of dermatological conditions and systemic disorders. Pruritus can broadly be classified into four categories: neuropathic, neurogenic/systemic, psychogenic, and pruritoceptive. Initial categorization depends on anatomical and pathophysiological aspects of presentation and is reflective of underlying etiology. We report a case of an 83-year-old man presenting with generalized pruritus secondary to cholestasis from bile duct malignancy. This case is notable for atypical presenting features, including a trunk eruption comprised of excoriated papules with onset following meloxicam initiation, mimicking a cutaneous adverse drug reaction. Providers should consider systemic etiologies of pruritus in patients presenting with cutaneous eruptions with atypical features. Accurate categorization of pruritus can facilitate treatment and/or additional investigation of systemic disease.
PubMed: 38116363
DOI: 10.7759/cureus.49049 -
Veterinary Anaesthesia and Analgesia Jan 2024To determine the pharmacokinetics of meloxicam in the nursehound shark (Scyliorhinus stellaris) during multiple dose administration.
OBJECTIVE
To determine the pharmacokinetics of meloxicam in the nursehound shark (Scyliorhinus stellaris) during multiple dose administration.
STUDY DESIGN
Prospective experimental trial.
ANIMALS
A total of eight clinically healthy adult nursehounds (four males, four females).
METHODS
Meloxicam was administered intramuscularly at a dose of 1.5 mg kg once daily for 7 days. Blood samples were collected from the caudal vein for pharmacokinetic analysis at 2.5 hours and 24 hours after drug administration. After a 4 week washout period, meloxicam was administered orally at the same dose at 12 hour intervals for three repeated doses. Blood samples were collected at 1, 2, 4, 6, 8, 12, 24, 36 and 48 hours after the first administration. Sharks were visually monitored during each study and 4 weeks afterwards for side effects or signs of toxicity. Time required to achieve steady state was assessed by visual inspection and statistical comparison of peak and trough concentrations using a Friedman test; comparison between sexes was performed using a Mann-Whitney U test and p-value was set at 0.05.
RESULTS
No animal died or showed clinical signs of toxicity during the study. Meloxicam administered orally did not produce detectable concentrations in plasma. After intramuscular administration, steady state was achieved after five doses, and mean trough and peak plasma concentrations at steady state were 1.76 ± 0.21 μg mL and 3.02 ± 0.23 μg mL, respectively. Mean peak concentration accumulation ratio was 2.50 ± 0.22.
CONCLUSIONS AND CLINICAL RELEVANCE
This study shows that intramuscular posology produces plasma concentrations considered therapeutic for other species. However, meloxicam was not detected in plasma after oral administration. These results suggest that meloxicam administered intramuscularly may be a useful non-steroid anti-inflammatory drug in nursehound sharks. Further pharmacodynamic studies are needed to fully evaluate its clinical use in this species.
Topics: Female; Male; Animals; Meloxicam; Sharks; Prospective Studies; Thiazines; Thiazoles; Half-Life; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Administration, Oral
PubMed: 38065822
DOI: 10.1016/j.vaa.2023.09.072 -
Pharmaceuticals (Basel, Switzerland) Oct 2023Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane...
Meloxicam (MX) is a nonsteroidal anti-inflammatory drug (NSAID) used mainly to reduce pain, inflammation, and fever. In the present study, thermosensitive polyurethane (PU)-based hydrogels with various excipients (PEG, PVP, HPC, and essential oil) were prepared and loaded with MX. Rheological investigations were carried out on the PU-based formulations in various shear regimes, and their viscoelastic characteristics were determined. The average size of the PU micelles was 35.8 nm at 37 °C and slightly increased at 37 nm in the presence of MX. The zeta potential values of the hydrogels were between -10 mV and -11.5 mV. At pH = 6 and temperature of 37 °C, the formulated PU-based hydrogels loaded with MX could deliver significant amounts of the active substance, between 60% and 80% over 24-48 h and more than 90% within 2 weeks. It was found that anomalous transport phenomena dominated MX's release mechanism from the PU-based networks. The results are encouraging for further studies aiming to design alternative carriers to commercial dosage forms of nonsteroidal anti-inflammatory drugs.
PubMed: 38004376
DOI: 10.3390/ph16111510