lornoxicam and Edema

Ethosomes, a novel type of percutaneous drug delivery carrier with a lipid bilayer structure, penetrate the skin barrier due to their deformability and malleability, and presence of ethanol that fluidizes lipids in the skin. In order to further enhance the delivery of drugs through the skin, penetration enhancers are widely used.. The objective of this work was to develop an optimized formulation of lornoxicam ethosomal gels, investigate skin permeability with the addition of penetration enhancers, and evaluate the invivo pharmacodynamics of these formulations.. Lornoxicam ethosomes were prepared by the ethanol injection method and optimized using the orthogonal design method. Lornoxicam ethosomal gels with enhancers were prepared and optimized using in-vitro transdermal delivery experiments. Experiments on lornoxicam ethosomal gels containing various enhancers such as azone, menthol, lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion cells to measure the percutaneous permeability of the different formulations. Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal gels were examined using the hot-plate and acetic acid-induced writhing tests. Anti-inflammatory activity was investigated using the dimethylbenzene-induced mouse ear swelling method.. The results showed that compared to other formulations, the optimized lornoxicam ethosomal gels with 5 % menthol significantly increased transdermal penetration. Meanwhile, the optimized lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti-inflammatory activity compared with the plain lornoxicam gels.. These results suggest that the optimized ethosomal gel formulated in this study is a promising lornoxicam carrier in transdermal delivery systems to enhance anti-nociceptive and antiinflammatory efficiency.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Drug Compounding; Drug Delivery Systems; Edema; Ethanol; Female; Gels; Hot Temperature; Lecithins; Liposomes; Menthol; Mice, Inbred BALB C; Pain; Piroxicam; Skin Absorption; Xylenes

The objective of this study was to investigate the potential of niosomal gels as a transdermal delivery system to improve the permeation and anti-inflammatory activity of Lornoxicam (LX).. LX niosomes were prepared by thin film hydration technique and were characterized using Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), Particle Size analysis and Zeta potential determination. LX niosomal gel/LX loaded gel were prepared using Carbopol 934 (2%) and were evaluated for their physical appearance, pH and rheological behaviour. Ex vivo skin permeation test was performed on dorsal region of wistar rats. In vivo studies comprised skin irritation test and anti-inflammatory activity study.. The prepared LX niosomes exhibited an entrapment efficiency of more than 66% and a particle size diameter ranging from 295 nm to 1298 nm, with negatively charged zeta potential. TEM electron micrographs revealed spherical shaped vesicles. The release pattern of drug was analyzed and found to follow Higuchi's model. Rheology studies revealed the pseudoplastic behaviour of LX niosomal gel. They exhibited a one and half fold increase in drug permeated through rat skin, when compared to free drug. Skin irritation test proved the non-irritancy of LX niosomal gels, when applied to dorsal region of Wistar rats. Percentage edema inhibition of LX niosomes was significantly higher (P<0.05) than that of free LX group showing an enhanced anti-inflammatory activity of LX niosomes.. These findings revealed that LX loaded niosomal gels could be a potential transdermal drug delivery system.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Drug Delivery Systems; Edema; Gels; Hydrogen-Ion Concentration; Kinetics; Liposomes; Particle Size; Piroxicam; Rats; Rats, Wistar; Rheology; Skin; Skin Absorption

Rheumatoid arthritis (RA) is a chronic inflammatory disease treated by nonsteroidal anti-inflammatory drugs (NSAIDs) including lornoxicam (LX). Nanocarriers have been used to increase the efficacy and reduce the side effects of various drugs. The objective of the present study was to compare the therapeutic efficacy of systemic administration of lornoxicam-loaded nanomicellar formula (LX-NM) with that of free LX.. The LX-loaded mixed polymeric nanomicellar formula was prepared by direct equilibrium technique. Two rat models were used in the study: carrageenan-induced acute edema and Freund's complete adjuvant (FCA)-induced chronic arthritis.. The inhibitory effect of LX-NM on carrageenan-induced edema was higher than free LX for the same dose (1.3 mg/kg, i.p.). LX-NM (0.325 mg/kg, i.p.) produced effects comparable to that of diclofenac, which served as a standard. In the FCA model, daily treatment with LX-NM (0.325 mg/kg, i.p.) starting on day 14 significantly reduced the percentage of edema and increased weight growth. However, the same dose of LX failed to confer any significant change. Additionally, LX-NM significantly attenuated the rise of tumor necrosis factor-α (TNF-α), interleukin-1β, prostaglandin E2, nuclear factor-κβ, malondialdehyde and nitric oxide serum levels. In contrast, LX failed to show any significant reduction in elevated serum biomarkers except for TNF-α.. LX-NM is an alternative delivery system that is simply prepared at low costs. It showed a superior therapeutic efficacy against RA compared to free LX. Thus, LX-NM can be considered as a promising candidate for treatment of RA and similar inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Carrageenan; Chronic Disease; Dinoprostone; Disease Models, Animal; Edema; Freund's Adjuvant; Interleukin-1beta; Male; Micelles; Nanoparticles; Piroxicam; Polymers; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

The present study investigates the drug delivery potential of polymer lipid hybrid nanocomposites (Lecithmer®) composed of poly(D,L-lactide-co-glycolide (PLGA) and soya lecithin. Core-shell structure of Lecithmer was evident from cryo-TEM images. Daunorubicin (DNR) and lornoxicam (LNX)-incorporated Lecithmer nanocomposites were evaluated for anticancer and anti-inflammatory activity. DNR- and LNX-loaded Lecithmer had mean particle size of ∼335 and ∼282.7 nm, respectively. Lecithmer formulated with different cationic lipids resulted in lower particle size (∼120 nm) and positive zeta potential. Entrapment efficiency of DNR and LNX was 93.16 and 88.59 %, respectively. In vitro release of DNR from Lecithmer was slower compared to PLGA nanoparticles. DNR release from Lecithmer was significantly higher at pH 5.5 (80.96 %) as compared to pH 7.4 (55.95 %), providing advantage for selective tumor therapy. Similarly, sustained release of LNX (30 % in 10 h) was observed at pH 7.4. DNR in Lecithmer showed superior cytotoxicity on human erythroleukemic K562 cells. Pharmacokinetic study in Wistar rats with i.v. administered DNR-loaded Lecithmer showed higher volume of distribution, lower elimination rate constant, and longer half-life (81.68 L, 0.3535 h(-1), 1.96 h) as compared to DNR solution (57.46 L, 0.4237 h(-1), 1.635 h). Pharmacodynamic evaluation of orally administered LNX-loaded Lecithmer showed superior anti-inflammatory activity with maximum inhibition of 81.2 % vis-à-vis 53.57 % in case of LNX suspension. In light of these results, Lecithmer can be envisaged as a promising nanosystem for parenteral as well as oral drug delivery.

Topics: Animals; Cell Survival; Cells, Cultured; Daunorubicin; Delayed-Action Preparations; Drug Delivery Systems; Drug Liberation; Edema; Humans; Lactic Acid; Lecithins; Male; Nanocomposites; Piroxicam; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats

The objective of this work was to increase the solubility, in vitro skin permeability of lornoxicam from semisolid topical formulations and also to investigate the in vivo potential of nanoemulsion formulation. Optimized lornoxicam loaded nanoemulsion was prepared successfully by spontaneous self-emulsification method and the size of the stable formulations was found within the range of 102 to 200 nm. The stable nanoemulsion formulations characterized for viscosity, droplet size, transmission electron microscopy (TEM) and refractive index. In vitro permeation rate of nanoemulsion and conventional gel of lornoxicam (LX) were determined. Prmeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion NE8 and the nanogel NG8 as compared to conventional gel (LG). In vivo studies revealed a significant increase in anti-inflammatory effects as compared with conventional gel of LX. The anti-inflammatory effects of formulation NG8 showed a significant increase in percent inhibition value when compared with control, this difference was found to be highly significant (p<0.001). This work shows for the first time that lornoxicam can be formulated into nanoemulsions and may show promise in enhancing solubility and permeation.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Disease Models, Animal; Edema; Emulsions; Freund's Adjuvant; Gels; Inflammation; Microscopy, Electron, Transmission; Nanomedicine; Nanoparticles; Particle Size; Permeability; Piroxicam; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility; Surface-Active Agents; Technology, Pharmaceutical; Viscosity

Transdermal patches of meloxicam (MX) and lornoxicam (LX) were aimed to be prepared in order to overcome their side effects by oral application. The strategy was formulation of optimized films to prepare transdermal patches by determination of physical properties and investigation of drug-excipient compatibility. As the next step, in vitro drug release, assesment of anti-inflammatory effect on Wistar Albino rats, ex vivo skin penetration and investigation of factors on drug release from transdermal patches were studied. Hydroxypropyl methylcellulose (HPMC) was concluded to be suitable polymer for formulation of MX and LX transdermal films indicating pharmaceutical quality required. MX and LX transdermal patches gave satisfactory results regarding to the edema inhibition in the assessment of anti-inflammatory effect. MX was found out to be more effective compared to LX on relieving of edema and swelling. These results were supported by data obtained from ex vivo penetration experiments of drug through rat skin. Indicative parameters like log P, molecular weight and solubility constraint on penetration rate of drugs also indicated good skin penetration. Transdermal patches of MX and LX can be suggested to be used especially for the immediate treatment of inflammated area since it displays anti-inflammatory effect, soon.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calorimetry, Differential Scanning; Drug Delivery Systems; Edema; Hypromellose Derivatives; Meloxicam; Methylcellulose; Piroxicam; Rats; Rats, Wistar; Skin; Spectroscopy, Fourier Transform Infrared; Tensile Strength; Thiazines; Thiazoles

Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effects of lornoxicam in relation to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain.. A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01-1 mg/kg), celecoxib (0.3-30 mg/kg) or loxoprofen (0.3-30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall-Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzyme-immunoassay.. In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen significantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it.. Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Celecoxib; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Extremities; Fever; Freund's Adjuvant; Hyperalgesia; Hypothalamus; Inflammation; Male; Pain Measurement; Phenylpropionates; Piroxicam; Pyrazoles; Rats; Rats, Inbred Lew; Rats, Wistar; Sulfonamides

To investigate the anti-inflammatory effect of preemptive intrathecal Lornoxicam on foot swelling of formalin test in rats.. Eighteen healthy male adult Sprague-Dawley (SD) rats (about 250 g) were randomized into 3 groups: intrathecal solvent group (group S, solvent 20 microL), intramuscular Lornoxicam group (group IM, Lornoxicam 300 microg/20 microL) and intrathecal Lornoxicam group (group IT, Lornoxicam 300 microg/20 microL). After measuring the basic volumes of the left hind paws, rats were injected with corresponding solution intrathecally or intramuscularly, and followed by an intra-plantar administration of 100 microL of 5% formalin 10 minutes later. The volumes of left hind paws were measured again at 10 min, 30 min, 1 h, 2 h, 3 h, 4 h, 24 h after formalin injection.. There was no statistical difference of weights or basic volumes among three groups. At 10 min after formalin injection, the left hind paw volume of group IT [(1.53 +/- 0.06) mL] were smaller than that of group S [(1.67 +/- 0.09) mL], P=0.039, but there was no statistically difference between group IT and group IM [(1.65 +/- 0.06) mL]. At 30 min after formalin injection, the left hind paw volume of group S [(1.88 +/- 0.88) mL] was larger than that of group IM [(1.77 +/- 0.05) mL, P<0.05] and group IT [(1.61 +/- 0.06) mL, P<0.01]. The feet swelling degree of group IT was less than that of group IM, P<0.05. At 1 h, 2 h and 3 h after formalin injection, the left hind paw volume of group S was similar to that of group IM, and the volume of group IT was smaller than the other two groups. At 4 h and 24 h after formalin injection, there were no statistic differences of the left hind paw volume among the three groups.. At 10 min to 3 h after formalin injection, swelling of rat feet induced by formalin was alleviated by preemptive intrathecal Lornoxicam.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Foot Diseases; Formaldehyde; Injections, Spinal; Male; Pain; Piroxicam; Random Allocation; Rats; Rats, Sprague-Dawley

A series of thiophene [3,2-b] pyrrole derivatives were synthesized and evaluated their abilities to inhibit anti-inflammatory activity. In this series, substituent effects at the N-1, 2 and 5 positions of thiophene [3,2-b] pyrrole were examined. The results obtained are compared to those previously reported anti-inflammatory drugs like Tenidap sodium, Diclofenac sodium and Piroxicam. The results indicated the critical role of the group linked in the N-1 position and 2, 5 positions of thiophene [3,2-b] pyrrole with different functional groups.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Male; Piroxicam; Pyrroles; Rats; Rats, Wistar; Structure-Activity Relationship; Thiophenes

To evaluate the anti-inflammatory/analgesic effects of lornoxicam in the carrageenan model of inflammatory nociception.. Three hours after intraplantar carrageenan (6 mg/150 microl of saline), we assessed the effects of pre-administered lornoxicam (0.1, 0.3, 1, 3 and 9 mg/kg i.v., n=10 rats for each group) on both the peripheral oedema and number of c-Fos-protein-like immunoreactive (c-Fos-LI) neurons in the lumbar L4-L5 segments, in the awake rat.. Lornoxicam dose-relatedly reduced both the carrageenan evoked oedema (r=0.63 and r=0.53 for paw and ankle diameter respectively; p<0.001 for both) and total number of spinal c-Fos-LI neurons (r=0.79; p<0.001), with the strongest effect corresponding to a 75 +/- 2% reduction of the number of c-Fos-LI neurons (p<0.001) for the highest dose (9 mg/kg), and a 45 +/- 3% reduction (p<0.001) for the low dose of 0.3 mg/kg. Reductions of both the peripheral oedema and spinal c-Fos expression were correlated (r=0.74 and r=0.57 for the paw and ankle diameter respectively; p<0.001 for both).. Our results demonstrate that lornoxicam reduces in parallel both the carrageenan-evoked oedema and spinal c-Fos expression, with clear evidence for a potent effect of low doses of lornoxicam. Correlated reductions in c-Fos expression and paw oedema suggest a predominantly peripheral site of action of lornoxicam.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cell Count; Edema; Inflammation; Male; Neurons; Nociceptors; Piroxicam; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Spinal Cord