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1.
AAPS PharmSciTech ; 24(1): 44, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703092

RESUMO

Tenoxicam (TX) is a non-steroidal anti-inflammatory agent that can be used to control pain in various ophthalmic lesions like cataracts, refractive surgery, and corneal abrasion. TX has a very slightly aqueous solubility of 0.072 mg/mL resulting in difficulty to be formulated in ophthalmic solutions. This study aims to improve TX solubility by converting it into its potassium salt to achieve a target of 10 mg/mL (1%w/v) concentration of TX in the desired aqueous medium for the formulation of aqueous ophthalmic solutions. The synthesized TX salt was characterized by different evaluation parameters such as solubility studies, 1H NMR, IR, and elemental analyses. Different TX potassium solutions were formulated at concentrations of 0.5% and 1% w/v using different viscosity-imparting agents. The prepared solutions were characterized for their physicochemical properties including visual inspection, pH, rheological, in vitro release, and kinetic behavior. Also, the formulations were biologically evaluated in vivo using male albino rabbits. The obtained results showed the successful synthesis of TX salt, as indicated by IR and NMR, and elemental analysis. The solubility study showed that the solubility of TX was improved hugely to 18 mg/mL (250-fold). In addition, the results showed that the prepared formulations showed acceptable physicochemical properties. The highest release rate was obtained with formula F1, which contains no viscosity-imparting agents. While as, the lowest release rate was obtained in the case of formula F9, composed of Pluronic F127 (12% w/v). The in vivo results showed that TX optimized ophthalmic solutions F8 and F9 inhibited the redness and edema in an extended or sustained manner.


Assuntos
Sistemas de Liberação de Medicamentos , Piroxicam , Animais , Masculino , Coelhos , Sistemas de Liberação de Medicamentos/métodos , Anti-Inflamatórios não Esteroides , Soluções Oftálmicas
2.
Environ Res ; 216(Pt 3): 114633, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343714

RESUMO

In this paper, an electrochemical sensor was developed to determine piroxicam (PX) and tramadole (Tr) based on their enhanced electrochemical responses at the surface of the polypyrrole/CuO nanocomposite-modified nanoporous gold film (NPGF) electrode. The experimental results showed that PX provide an oxidation peak at 0.65 V in pH = 8.0. The DPV results were linearly affiliated on PX concentration within the two closed windows (C1PX = 0.05-30.0 µM, correlation coefficient of 0.9905, and C2PX = 50.0-300.0 µM, correlation coefficient of 0.9927). From voltammetric curves, the detection limit (LOD = 3Sb/m) for PX at a surface of PPY-CuO-NPGF electrode was appeared to be 0.01 µM. Furthermore, the ability of PPY-CuO-NPGF electrode for simultaneous measurement of PX and Tr was investigated. The suggested sensor shows a long-time stability, good repeatability, and rapid response in the mixture media of PX and Tr.


Assuntos
Nanocompostos , Nanoporos , Ouro , Polímeros , Pirróis , Piroxicam , Técnicas Eletroquímicas/métodos
3.
Sci Rep ; 12(1): 19806, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36396965

RESUMO

Dexamethasone, a common medication used in the treatment regimen of glioblastoma, has broad inhibitory effects on the immune responses. Here, in an in vitro study, we examined the effects of piroxicam, a potent substitute for dexamethasone, on peripheral blood mononuclear cells (PBMCs) co-cultured with two glioblastoma cell lines, U-87 MG and A-172 cells. MTT assay was used to determine the proliferation of PBMCs treated with piroxicam, or dexamethasone. In addition, to evaluate the effects of drugs on the cell cycle distribution, DNA content per cell was analyzed in PBMCs and A-172 cell lines using flow cytometry. Oxidative parameters, including superoxide dismutase-3 (SOD3) activity and total anti-antioxidant capacity, lactate dehydrogenase (LDH) activity, as well as IFN-γ and TGF-ß levels were measured in PBMCs alone or in the presence of cell lines using ELISA. Unlike dexamethasone, piroxicam showed a protective effect on PBMCs against both glioblastoma cell lines. Furthermore, while dexamethasone reduced the proliferation of PBMCs, piroxicam had no adverse effect on the proliferation. Cell cycle analysis showed a reduction in the G2/M phase in piroxicam-treated A-172 cells. Additionally, dexamethasone limited the cell cycle progression by increasing the fraction of PBMCs in G0/G1. Interestingly, after co-culturing piroxicam-treated PBMCs with cell lines, a remarkable rise in the LDH activity was observed. Although not significant, piroxicam partially decreased TGF-ß levels in both cell lines. Our findings suggested a protective effect of piroxicam, but not dexamethasone, on PBMCs against inhibitory mechanisms of two glioblastoma cell lines, U-87 and A-172 cells.


Assuntos
Glioblastoma , Leucócitos Mononucleares , Humanos , Leucócitos Mononucleares/metabolismo , Piroxicam/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Linhagem Celular , Fator de Crescimento Transformador beta/metabolismo
4.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36232651

RESUMO

Actinic keratosis is an intraepithelial proliferation of atypical keratinocytes that could progress into invasive squamous cell carcinoma. Most evidence suggests an important role of the dermal matrix metalloproteinases in the progression of atypical skin epithelial lesions. We evaluated the clinical efficacy of three different therapeutic modalities (a medical device containing 0.8% piroxicam cream and 50+ sunscreen, photodynamic therapy, and ingenol mebutate gel) to treat suspicious actinic keratoses, which were biopsied for histopathological examination and then analyzed for the expression of matrix metalloproteinases by immunohistochemistry. Clinical, dermoscopic, and reflectance confocal microscopy evaluations revealed a gradual decrease in all standard scores validated for actinic keratosis assessment at the end of the treatments. From a histopathological point of view, we documented the substantial restoration of normal skin architecture, while the immunohistochemical evaluation of matrix metalloproteinases showed a reduction in expression in the treated skin lesions compared to the baseline. As actinic keratoses are considered the precursors of squamous cell carcinoma, their treatment is crucial to prevent the development of a more aggressive disease. Our study monitored the evolution of actinic keratoses subjected to three different topical therapies, with the value of correlating clinical and histopathological findings. Moreover, as the matrix metalloproteinases are largely recognized factors involved in the pathogenesis and evolution of actinic keratosis to squamous cell carcinoma, the demonstration by immunohistochemistry of a reduction in their expression after the treatments adds new valuable concern to the field.


Assuntos
Carcinoma de Células Escamosas , Diterpenos , Ceratose Actínica , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Ceratose Actínica/tratamento farmacológico , Ceratose Actínica/patologia , Metaloproteases/uso terapêutico , Piroxicam , Estudos Retrospectivos , Protetores Solares , Resultado do Tratamento
5.
Eur Endod J ; 7(3): 187-192, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36217645

RESUMO

OBJECTIVE: The objective of this study was to compare the effectiveness of premedication drugs including single dose Piroxicam and Prednisolone in regard to post endodontic pain at different time intervals (24, 48, 72 and 96 hours) after single visit root canal treatment. METHODS: This randomized clinical trial (registration no. NCT04124822) was performed in operative dentistry department of a private clinical institute. One hundred twenty patients identified with symptomatic irreversible pulpitis were included in the study. The pain intensity levels were marked through the use of visual analog scale (VAS) before the commencement of treatment. The participants were randomly allocated in three groups, Group I (n=40) received no medication (control), Group II (n=40) received Piroxicam (20 mg) and Group III (n=40) received Prednisolone (20 mg). The drugs were administered thirty minutes before the endodontic procedure was initiated. Root canal treatmentwas carried out followed by placement of provisional restoration in a single appointment. The patients were instructed to continue marking their pain intensity levels after 24, 48, 72 and 96 hours using VAS. All patients were called for follow up after 4 days for clinical evaluation and the placement of permanent restoration. The effectiveness of each drug over different time interval was studied employing ANOVA test. The significance level was set at P≤0.05. RESULTS: The results of the present study revealed that a higher percentage of patients in all 3 groups, reported no post-operative pain at all evaluated time durations (24, 48, 72, and 96 hours). However, the long term effectiveness (96 hours) of both drugs to reduce post-endodontic pain was observed to be statistically insignificant. There was no significant difference in demographic data in terms of age (P=0.14), gender (P=0.12), whilst tooth type (P≤0.05) showed statistically significant value. CONCLUSION: Pre-medication with either single dose piroxicam or prednisolone was able to prevent post-endodontic pain in patients with symptomatic irreversible pulpitis.


Assuntos
Piroxicam , Pulpite , Cavidade Pulpar , Humanos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Piroxicam/uso terapêutico , Prednisolona/uso terapêutico , Pré-Medicação , Pulpite/terapia
6.
J Chem Inf Model ; 62(19): 4760-4770, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36126250

RESUMO

Human carbonic anhydrase VII (hCA VII) constitutes a promising molecular target for the treatment of epileptic seizures and other central nervous system disorders due to its almost exclusive expression in neurons. Achieving isoform selectivity is one of the main challenges for the discovery of new hCA inhibitors, since nonspecific inhibition may lead to tolerance and side effects. In the present work, we report the development of a molecular docking protocol based on AutoDock4Zn for the search of new hCA VII inhibitors by virtual screening. The docking protocol was applied to the screening of two sets of compounds: a ZINC15 subset of sulfur-containing structures and an in-house library consisting of synthetic and commercial candidates (including approved drugs). Five compounds were selected from the first screening campaign and three from the second one, and they were tested in vitro against the enzyme. Among the eight selected structures, four showed Ki values in the low nanomolar range. These confirmed hits include three approved drugs: meloxicam, piroxicam, and nitrofurantoin, which also showed good selectivity for hCA VII versus hCA II.


Assuntos
Inibidores da Anidrase Carbônica , Anidrases Carbônicas , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/química , Humanos , Meloxicam , Simulação de Acoplamento Molecular , Estrutura Molecular , Nitrofurantoína , Piroxicam , Isoformas de Proteínas/metabolismo , Relação Estrutura-Atividade , Sulfonamidas/química , Enxofre
7.
J Pharm Sci ; 111(11): 3174-3184, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36057318

RESUMO

Lornoxicam physiologically based pharmacokinetic (PBPK) models were developed and validated on the basis of clinical pharmacokinetic results obtained by considering CYP2C9 genetic polymorphisms in healthy adult populations. PBPK models were extended to predict lornoxicam pharmacokinetics for patients with cirrhosis by quantitatively examining the pathophysiological information associated with cirrhosis. The predicted plasma exposure to lornoxicam was approximately 1.12-2.83 times higher in the CYP2C9*1/*3 and *1/*13 groups than in the CYP2C9*1/*1 group of healthy adult populations and patients with cirrhosis. The predicted plasma exposure to lornoxicam was approximately 1.28-3.61 times higher in patients with cirrhosis than in healthy adult populations. If the relationship between lornoxicam exposure in plasma and drug efficacy was proportional, then the proposed adjusted doses of lornoxicam for each group varied from 1.25 mg to 8 mg. As the severity of cirrhosis increased, or when the CYP2C9 genotype was *1 heterozygous, the dose adjustment range of lornoxicam increased. Therefore, the effect of pathophysiological factors (cirrhosis severity) on the pharmacokinetics of lornoxicam might be more important than that of CYP2C9 genetic factors. These results could be useful for broadening the scope of clinical application of lornoxicam by enabling dose selection based on CYP2C9 genotypes and liver cirrhosis degree.


Assuntos
Citocromo P-450 CYP2C9 , Cirrose Hepática , Piroxicam , Adulto , Citocromo P-450 CYP2C9/genética , Genótipo , Humanos , Cirrose Hepática/tratamento farmacológico , Modelos Biológicos , Piroxicam/administração & dosagem , Piroxicam/análogos & derivados , Piroxicam/farmacocinética
8.
Inflammopharmacology ; 30(6): 2097-2106, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36085399

RESUMO

Piroxicam is used to treat the pain, swelling, and stiffness associated with osteoarthritis and rheumatoid arthritis, but it has many side effects, such as hypertension, elevation of liver enzymes, and hepatitis. This study used selenium-enriched probiotics to reduce the side effects of piroxicam on the liver and kidney tissues and functions. Forty-eight male albino mice were randomly assigned to control, piroxicam (P), piroxicam plus selenium-enriched Lactobacillus plantarum PSe40/60/1 (P + SP), piroxicam plus selenium-enriched Bifidobacterium longum BSe50/20/1 (P + SB), selenium-enriched L. plantarum PSe40/60/1 (SP), and selenium-enriched B. longum BSe50/20/1 (SB) groups. In this study, the function of the liver and kidney was biochemically determined; the histopathology of the liver and kidney tissues was microscopically examined and the expression of inflammatory and anti-inflammatory genes in liver and kidney tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Liver and kidney functions were significantly reduced in the piroxicam group compared with control. Liver and kidney tissues were damaged in the piroxicam group while they appeared more or less normal in the SB group. The expression of inflammatory genes was significantly up-regulated in the liver and kidney tissues of the piroxicam group compared to the control group. The expression of anti-inflammatory genes was significantly down-regulated in the liver and kidney of the piroxicam group and up-regulated in the liver and kidney of the SB group compared to the control group. Therefore, these mutated strains of probiotics were useful in reducing the side effects of the piroxicam drug on the liver and kidney.


Assuntos
Probióticos , Selênio , Animais , Camundongos , Masculino , Selênio/farmacologia , Piroxicam/farmacologia , Probióticos/farmacologia , Fígado , Rim/metabolismo
9.
Biomed Res Int ; 2022: 1546734, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958816

RESUMO

Lornoxicam is a potent oxicam-class nonsteroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory, and antipyretic effects. Its impacts on many biological functions are not fully understood. We measured various biomarkers in male albino rats provided an oral aqueous ginger extract before IM administration of therapeutic and 2× the therapeutic doses of lornoxicam. The aqueous ginger plant extract was characterized by mass spectroscopy, and its effects were determined by examining free radical scavenging activity, blood parameters, renal and hepatic function, semen quality, proinflammatory cytokines, antioxidant markers, and histopathology. Rats administered lornoxicam had significantly higher liver and kidney function biomarker values, TNF-α, interleukin-6, and sperm abnormalities than the control rats. The overall erythrocyte count, packed cell volume, prostaglandin, and sperm counts were all considerably lower in the experimental animals. Histological changes were found in the liver, spleen, and testes of rats administered lornoxicam alone. In rats, pretreatment with ginger extract reduced the majority of the negative effects of conventional and high dosages of lornoxicam.


Assuntos
Anti-Inflamatórios , Gengibre , Rizoma , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Gengibre/química , Masculino , Piroxicam/análogos & derivados , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Rizoma/química , Análise do Sêmen
10.
J Ethnopharmacol ; 298: 115660, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35995277

RESUMO

ETHNOPHARMACOLOGICAL IMPORTANCE: Casearia sylvestris Sw. (Salicaceae) is a native plant from the Americas, where it is also known as "guaçatonga" or "erva-de-bugre." Although its leaves have been commonly used to treat inflammation and gastrointestinal disorders in South America, the antiulcer effects of an aqueous extract from this medicinal plant, similar to popular use, have not to be investigated yet. AIM OF THE STUDY: This study evaluated the hypothesis that the aqueous extract a of C. sylvestris (AEC) prevents the gastric ulcers and accelerates the healing of ulcers already installed, by assessing ultrasound imaging, histological and biochemical analyses. MATERIALS AND METHODS: Rats (females) were treated with AEC (3, 30 or 300 mg/kg) prior to the ethanol or piroxicam-induced gastric ulcers. The healing effect of AEC (300 mg/kg) was examined in 80% acetic acid-induced ulcer in rats, whereas the quality of healing was evaluated in recurrent 10% acetic acid-induced ulcer in mice with recurrence induced by interleukin 1ß. To assess the responses of the lesions, in addition to the classical methods used to analyze gastroprotection (ex vivo), we also measured the gastric wall thickness (in vivo) using ultrasonography. After euthanasia, the extent of ulcer was determined and the levels of reduced glutathione (GSH), lipid hydroperoxides (LOOH), nitrate, and the activities of myeloperoxidase (MPO), N-acetyl-ß-D-glycosaminidase (NAG), superoxide dismutase (SOD), and glutathione S-transferase (GST) were measured. The antisecretory activity of AEC was also examined based on pylorus ligated rats. Furthermore, gastric tissue samples were analyzed histologically, and phytochemical analyses of the C. sylvestris extract were parallelly performed. RESULTS: The AEC (30 or 300 mg/kg) prevented ulcers in the ethanol- and piroxicam-induced acute. Moreover, the AEC at a dose of 300 mg/kg also accelerated the gastric healing of acetic acid-induced ulcer in rats by 48% and the ultrasonography records shown a decrease in the wall thickness and the extent of edema of ulcerous lesions promoted by the extract. The gastric healing effect of AEC was also accompanied by reduced MPO and NAG activities at acetic acid-induced ulcer in rats; as well as was by the reduction in the nitrate and LOOH levels, the increase in mucin and SOD activity, and by a partial recovery of GSH levels. The AEC (300 mg/kg) minimized the ulcer recurrence in mice exposed to IL-1ß, but the extract administration did not change pH or peptic activity of gastric juice in pylorus ligated rats. CONCLUSION: The results of this study provide convincing evidence for the therapeutic efficacy of C. sylvestris with respect to gastroprotection and indicate that ultrasound examination would be a potentially promising approach for evaluating gastroprotective effects in vivo. Collectively, our findings indicate that the gastric the gastroprotective and healing effects of aqueous extract C. sylvestris involve a reduction in acid secretion, promotion of the antioxidant system, reductions in the migration of neutrophils and mast cells, with a consequent lower inflammatory response, and the preservation of mucin.


Assuntos
Antiulcerosos , Casearia , Úlcera Gástrica , Ácido Acético/uso terapêutico , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol/farmacologia , Feminino , Mucosa Gástrica , Camundongos , Mucinas , Nitratos , Fitoterapia , Piroxicam/efeitos adversos , Extratos Vegetais/efeitos adversos , Ratos , Ratos Wistar , Roedores , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Superóxido Dismutase , Úlcera/tratamento farmacológico , Ultrassonografia
11.
Int J Pharm ; 624: 122006, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35820515

RESUMO

Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II) and a short half-life (3-4 h). Mucoadhesive buccal tablets containing LRX -loaded solid lipid nanoparticles (SLNs) were developed to enhance the drug solubility and bioavailability and achieve a controlled release pattern for a better anti-inflammatory effect. Different LRX-loaded SLNs were prepared using the hot homogenization /ultra-sonication technique and evaluated using size analysis and entrapment efficiency (EE%). Optimized LRX -loaded SLNs formulation showed particle size of 216 ± 7.4 nm, zeta potential of -27.3 ± 4.6 mV, and entrapment efficiency of 92.56 ± 2.3 %. Dried LRX-loaded SLNs alongside mucoadhesive polymers blend (PVP K30 /HPMC K15) were compressed to prepare the mucoadhesive buccal tablets. The tablets showed proper physicochemical properties, good mucoadhesive strength, long mucoadhesive time, suitable pH surface, good swelling capacity, and controlled drug release profile. Furthermore, Fourier transform-infrared (FTIR) spectroscopy, Powder X-Ray diffraction (PXRD), and Scanning electron microscopy (SEM) studies were carried out. The in vivo anti-inflammatory effect of pure LRX, market LRX and optimized mucoadhesive buccal tablet of LRX -loaded SLNs (T3) against carrageenan-induced models were evaluated. T3 showed a significant and early anti-inflammatory response after 1 and 2 h (63.62-77.84 % inhibition) as well as an extended effect after 4 h as compared to pure and market LRX. In parallel, T3 showed the best amelioration of PGE2, COX2, and TNF-α serum levels after 4 h of carrageenan injection.


Assuntos
Lipídeos , Nanopartículas , Anti-Inflamatórios , Carragenina , Portadores de Fármacos/química , Humanos , Inflamação/tratamento farmacológico , Lipídeos/química , Lipossomos , Nanopartículas/química , Tamanho da Partícula , Piroxicam/análogos & derivados , Comprimidos
12.
Artigo em Russo | MEDLINE | ID: mdl-35904290

RESUMO

Nonsteroidal anti-inflammatory drugs (NSAIDs) are traditionally used to relieve pain syndromes. The class of NSAIDs includes oxicams (meloxicam, tenoxicam, lornoxicam) - drugs with pronounced analgesic and anti-inflammatory effects. Oxicams have common properties of the class, but at the same time, due to structural differences from all other NSAIDs, they differ in a number of clinical and pharmacological characteristics, knowledge of which will help to individualize the choice of the drug.


Assuntos
Anti-Inflamatórios não Esteroides , Tiazinas , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Meloxicam , Piroxicam/farmacologia , Piroxicam/uso terapêutico
13.
J Pharm Biomed Anal ; 219: 114966, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-35908414

RESUMO

The aim of the present study is to develop the polymeric nanoparticulate drug delivery systems of piroxicam and to evaluate the in-vitro characteristics such as entrapment efficiency, surface morphology, in-vitro drug release performance, etc. For this reason, a novel HPLC methodology was developed for the determination of piroxicam from its bulk form, pharmaceutical preparation, and nanoparticulate delivery systems. Furthermore, the developed formulation was applied to the rats and the biological samples (plasma, liver, heart, spleen, kidney, and lung homogenates) were analyzed by the developed HPLC method following a salting-out assisted liquid-liquid extraction strategy for the first time in the literature. A Kinetex C18 analytical column (150 mm × 4.6 mm i.d., 5 µm) was used as a stationary phase with a 0.8 mL/min flow rate of acetonitrile: phosphate buffer (40:60, v/v), the column oven was adjusted to 40 °C and detection wavelength is set to 360 nm. Developed method were validated as per selectivity, linearity, LOD, LOQ, precision, and accuracy specified in the International Council for Harmonisation guidelines. As a result of the present study, it has been shown that the analysis of piroxicam from the bulk form, pharmaceutical preparation, developed polymeric-based drug delivery system, and biological samples can be successfully performed and no interferences were observed in any matrix. The developed method was also successfully utilized to study the tissue distribution of piroxicam in rats.


Assuntos
Extração Líquido-Líquido , Piroxicam , Animais , Cromatografia Líquida de Alta Pressão/métodos , Extração Líquido-Líquido/métodos , Preparações Farmacêuticas , Polímeros , Ratos
14.
Int J Pharm ; 624: 122060, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-35905932

RESUMO

Lornoxicam (LOR), a BCS II nonsteroidal anti-inflammatory drug, has been clinically utilized for moderate to severe acute pain management. However, it has poor water solubility and insufficient tabletability, leading to erratic absorption and challenge in tablet processability. This study reported a novel solid state of LOR (i.e., LOR sodium chelate monohydrate, LOR-Na·H2O) with significantly improved solubility, dissolution rate and tabletability. The prepared chelate (CCDC No.: 2125157) contains LOR-, Na+, and H2O in a molar ratio of 1:1:1, where Na+ ions bridged with O(5) of amide group, and N(2) of pyridine group on LOR-, as well as O(4) on H2O through coordination bonds. LOR-Na·H2O displayed a superior dissolution rate (5 âˆ¼ 465 folds) than commercial LOR due to its increased wettability (contact angle: 74.5° vs 85.6°) and lower solvation free energy (∼2-fold). In addition, the significant improvement in tabletability was caused by high plasticity and deformability, which was attributed to its special interlayer gliding with weak bonding interactions across layers but strong coordination bonding interactions within layers. The novel LOR-Na·H2O with significantly enhanced pharmaceutical performance offers a promising strategy for further product development.


Assuntos
Piroxicam , Sódio , Piroxicam/análogos & derivados , Piroxicam/química , Solubilidade , Comprimidos
15.
Biomarkers ; 27(8): 727-742, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35837760

RESUMO

INTRODUCTION: Fruits of Ammi majus, commonly called bishop's weed, contain a significant amount of furanocoumarins. Alloimperatorin (Allo, 6) was isolated from the free coumarin fraction of fruits, beside 8-hydroxypsoralen (1), methoxsalen (2), heraclin (3), isoimperatorin (4), imperatorin (5), isoheraclenin (7) and heraclenin hydrate (8). Piroxicam (Px) is a widely used pain-relieving drug that demonstrated side effects, including gastric ulceration and hepatorenal toxicity. OBJECTIVE: This study aimed to investigate the protective potential of Alloimperatorin against Px-induced gastric ulceration and hepatorenal toxicity. MATERIAL & METHODS: Rats were divided into four groups: Negative control, Px-induced rats, Allo + Px co-treated group, and Pc + Px co-treated group. Allo (25 mg/kg body weight) and Pc (25 mg/kg body weight) treatments were received 5 days before and 4 days after Px intoxication for 4 days (50 mg/kg body weight). Serum prostaglandin E2 (PG-E2) and liver and kidney functions were measured. Oxidative stress markers were evaluated in the three tissues. Histopathological features and caspase-3 immunoexpression were monitored. RESULTS & DISCUSSION: Px triggered gastric ulceration, increased indices of liver and kidney functions, decreased PG-E2 levels, provoked oxidative stress, and activated caspase-3 immunoexpression. Co-treatment with Allo demonstrated protective activities. CONCLUSION: Alloimperatorin exhibited anti-oxidative, anti-inflammatory, and anti-apoptotic activities.


Assuntos
Ammi , Úlcera Gástrica , Animais , Ratos , Apoptose , Peso Corporal , Caspase 3/metabolismo , Frutas , Fígado/metabolismo , Estresse Oxidativo , Piroxicam/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo
16.
Int J Biol Macromol ; 209(Pt B): 2084-2096, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500769

RESUMO

This study presents new drug delivery systems based on xanthan, unmodified or modified by esterification with oleic acid, and alginate for controlled release of bioactive substances with anti-inflammatory (piroxicam) and antifungal properties (ketoconazole). The mechanical properties of the developed drug carriers showed that their compressive strength was affected by the encapsulation of the bioactive principles. When ketoconazole was added into the xanthan/alginate matrix, an increment in the mechanical strength was recorded (66.68% compression). The release of the active principles from the materials was best described by the Korsmeyer-Peppas model, with non-Fickian or Fickian diffusion (the values of the exponent of release are between 0.29 and 0.75), depending on the composition of the polymeric matrix. The release rate constant presents smaller values for the materials based on chemically modified xanthan (between 0.89 and 20.11) as compared with materials based on the unmodified form (between 4.27 and 25.00). All materials were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The designed systems prove to have antimicrobial and anti-inflammatory activity. The findings make prone these biomaterials for the manufacture of transdermal drug delivery systems.


Assuntos
Alginatos , Piroxicam , Alginatos/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Excipientes , Cetoconazol , Polissacarídeos Bacterianos , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Arch Pharm Res ; 45(5): 352-366, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35639246

RESUMO

Piroxicam is a non-steroidal anti-inflammatory drug used to alleviate symptoms of osteoarthritis and rheumatoid arthritis. CYP2C9 genetic polymorphism significantly influences the pharmacokinetics of piroxicam. The objective of this study was to develop and validate the piroxicam physiologically based pharmacokinetic (PBPK) model related to CYP2C9 genetic polymorphism. PK-Sim® version 10.0 was used for the PBPK modeling. The PBPK model was evaluated by predicted and observed plasma concentration-time profiles, fold errors of predicted to observed pharmacokinetic parameters, and a goodness-of-fit plot. The turnover number (kcat) of CYP2C9 was adjusted to capture the pharmacokinetics of piroxicam in different CYP2C9 genotypes. The population PBPK model overall accurately described and predicted the plasma concentration-time profiles in different CYP2C9 genotypes. In our simulations, predicted AUCinf in CYP2C9*1/*2, CYP2C9*1/*3, and CYP2C9*3/*3 genotypes were 1.83-, 2.07-, and 6.43-fold higher than CYP2C9*1/*1 genotype, respectively. All fold error values for AUC, Cmax, and t1/2 were included in the acceptance criterion with the ranges of 0.57-1.59, 0.63-1.39, and 0.65-1.51, respectively. The range of fold error values for predicted versus observed plasma concentrations was 0.11-3.13. 93.9% of fold error values were within the two-fold range. Average fold error, absolute average fold error, and root mean square error were 0.93, 1.27, and 0.72, respectively. Our model accurately captured the pharmacokinetic alterations of piroxicam according to CYP2C9 genetic polymorphism.


Assuntos
Modelos Biológicos , Piroxicam , Anti-Inflamatórios não Esteroides , Citocromo P-450 CYP2C9/genética , Polimorfismo Genético
18.
J Pharm Biomed Anal ; 216: 114799, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35525111

RESUMO

In the present research, piroxicam entrapped core-shell lipid-polymer hybrid nanocarriers were developed and also evaluated in terms of nanoparticle features and cell-based in vitro efficacy on prostate cancer cells. Box-Behnken optimization approach was implemented to evaluate the impact of the input variables, namely phospholipid/PLGA ratio, total lipids/lecithin molar ratio, and piroxicam concentration, on two output variables: particle size and entrapment efficiency. Surface charge, size distribution, morphological structure of particles, drug release profiles, presence of outer lipid shell, thermal profile and possible interactions and storage stability of core-shell nanocarriers of piroxicam were studied as particle features. Cell viability, apoptosis and cell cycle arrest studies were utilized for in vitro cell-based evaluation of the core-shell nanosystems. The hybrid nanocarrier formulation with a particle size of 119.2 nm and an entrapment efficiency of 91.7% at the center point of the design was selected as the optimized formulation according to the desired function (d) method applied within the scope of the Box-Behnken design approach and RSM strategy. The cell viability and apoptosis experiments were performed on the optimized nanocarrier. In conclusion, this study demonstrates that the optimized core-shell nanoformulation of piroxicam is a more promising strategy in the treatment of prostate cancer compared to the pure molecule.


Assuntos
Nanopartículas , Neoplasias da Próstata , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Lecitinas , Masculino , Nanopartículas/química , Tamanho da Partícula , Piroxicam/farmacologia , Neoplasias da Próstata/tratamento farmacológico
19.
Drug Deliv ; 29(1): 1423-1436, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35532141

RESUMO

Intra-articular (IA) injection is grasping much interest due to the poor drug bioavailability at the targeted site of action which minimizes the effect of the orally administered moiety. Based on the integral role of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of Rheumatoid Arthritis (RA), much effort is exerted to develop novel localized drug delivery systems to increase their bioavailability and minimize their side effects. Artificial intelligence (AI) is acquiring an increasing role in the design of experiments being an effective tool for saving both time and resources. Hence, the aim of this work was to develop, characterize and optimize targeted in-situ forming nano particles (ISNs) for IA delivery of piroxicam using Design® Expert as an AI-based application where a 33 full factorial experimental design was adopted. Morphological investigation, injectability, rheological studies, Fourier Transform Infrared Radiation (FTIR) as well as biological, histopathological, and biochemical examinations were performed to evaluate the optimized-ISNs. The optimized formulation, exhibiting a nano-sized particle size with a dense core, showed significant improvement in the histopathological findings compared to both the oral solution and the placebo. Additionally, the once-a-week IA administration of the optimized-ISNs proved a significant reduction in the protein expression of both STAT-3 and RANKL and the levels of anti-CCP and MCP-1 by almost 54 and 73%, respectively, coupled with a marked decline in the content of IL-17, MMP-3, NF-κB and TNF-α as compared to the positive control. In conclusion, the use of ISNs for intra-articular injection has demonstrated their effectiveness in piroxicam delivery for RA treatment.


Assuntos
Artrite Reumatoide , Nanopartículas , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Inteligência Artificial , Sistemas de Liberação de Medicamentos , Humanos , Injeções Intra-Articulares , Nanopartículas/química , Piroxicam
20.
J Appl Microbiol ; 133(4): 2182-2197, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35503000

RESUMO

AIM: Quorum sensing (QS) inhibition is a promising strategy to suppress bacterial virulence and control infection caused by Gram-negative and Gram-positive bacteria. This study explores the QS inhibiting activity of the non-steroidal anti-inflammatory drugs (NSAIDs) in Acinetobacter baumannii. METHODS AND RESULTS: Ketoprofen, piroxicam and indomethacin revealed QS inhibition via elimination of violacein production of the reporter strain Chromobacterium violaceum ATCC 12472 without affecting bacterial growth. The minimal inhibitory concentration (MIC) of ketoprofen, piroxicam and indomethacin was determined against A. baumannii strains ATCC 17978, ATCC 19606, A1, A11 and A27 by the microbroth dilution method. The MICs of ketoprofen against tested isolates were 0.7-6.25 mg ml-1 , piroxicam MICs were 1.25-2.5 mg ml-1 , and indomethacin MICs were 3.12-12.5 mg ml-1 . Those compounds significantly inhibited QS-associated virulence factors such as biofilm formation, and surface motility, as well as, significantly increased bacterial tolerance to oxidative stress without affecting bacterial growth. On the molecular level, the three compounds significantly inhibited the transcription of QS regulatory genes abaI/abaR and biofilm-regulated genes cusD and pgaB. Molecular docking analysis revealed the potent binding affinity of the three compounds with AbaI via hydrogen and/or hydrophobic bonds. CONCLUSION: These results indicate that NSAIDs, ketoprofen, piroxicam and indomethacin, could be potential inhibitors of the QS and could suppress the QS-related virulence factors of A. baumannii. SIGNIFICANCE AND IMPACT: Ketoprofen, piroxicam and indomethacin could provide promising implications and strategies for combating the virulence and pathogenesis of A. baumannii.


Assuntos
Acinetobacter baumannii , Cetoprofeno , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Biofilmes , Chromobacterium/metabolismo , Hidrogênio , Indometacina/farmacologia , Cetoprofeno/farmacologia , Simulação de Acoplamento Molecular , Piroxicam/farmacologia , Percepção de Quorum , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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