RESUMO
The widespread occurence of pharmaceutical pollutants seriously threatens the environment and human well-being. In the present study, zinc ferrite nanoparticles (ZnFe2O4 NPs) have been synthesized by co-precipitation method and used as photocatalyst for the degradation of two most commonly prescribed painkillers, piroxicam (PXM) and paracetamol (PCM), via heterogeneous Fenton process under the solar light. The synthesized ZnFe2O4 NPs showed a narrower band gap i.e. 1.87 eV, signifying the ability to efficiently work in visible light range. In context of photocatalytic applications, the operational conditions were optimized to achieve maximum degradation. PCM and PXM were completely degraded (100%) at the optimized photocatalytic dose (20 mg L-1), reaction time (180 min), initial drug concentration (10 mg L-1), and pH (6.0), which is close to the natural environment. The extent of mineralization as estimated by the reduction of total organic carbon (TOC) was observed to be â¼91 and 82% for PCM and PXM respectively. Kinetic studies revealed that photocatalytic degradation followed pseudo-first-order kinetics. Moreover, the ZnFe2O4 NPs retained â¼90 % of photocatalytic activity after five consecutive reaction cycles, showing remarkable reusability and stability of catalyst.
Assuntos
Acetaminofen , Peróxido de Hidrogênio , Piroxicam , Luz Solar , Poluentes Químicos da Água , Acetaminofen/química , Piroxicam/química , Catálise , Poluentes Químicos da Água/química , Peróxido de Hidrogênio/química , Fotólise , Ferro/química , Compostos Férricos/química , Cinética , Zinco/químicaRESUMO
Aim: This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Materials & methods: Synthesized nanoparticles were subjected to in vitro characterization, ex vivo permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. Results & conclusion: The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.
[Box: see text].
Assuntos
Administração Cutânea , Nanopartículas , Piroxicam , Polietilenoglicóis , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Piroxicam/análogos & derivados , Piroxicam/administração & dosagem , Piroxicam/química , Polietilenoglicóis/química , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Humanos , Portadores de Fármacos/química , Tamanho da Partícula , Inflamação/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Camundongos , Ácido Láctico/química , Masculino , Ratos , Ácido Poliglicólico/química , Pele/metabolismo , Pele/efeitos dos fármacosRESUMO
Piroxicam (PX) is a nonsteroidal anti-inflammatory drug (NSAID) commonly associated with gastrointestinal (GI) injuries, including dyspepsia, heartburn, inflammation, bleeding, ulceration, and life-threatening perforation. The ß-cyclodextrin (ß-CD)-based PX formulation (PX@CD) has been shown to reduce gastric side effects by improving PX's solubility and dissolution rates. However, the solubility of PX can only be increased to a limited extent by ß-CD, due to the low binding constant between PX and ß-CD (â¼100 M-1). As a result, adverse reactions such as epigastric pain and pyrosis are still commonly reported. Cucurbit[7]uril (CB[7]) is a synthetic macrocyclic host compound that binds strongly to various drugs. In this study, we demonstrated that CB[7] forms complexes with PX in the gastric acid environment with a binding constant approximately 70 times higher than that between ß-CD and PX. The PX@CB[7] inclusion complexes exhibited rapid dissolution rates in the gastric environment. In addition, PX@CB[7] showed significantly higher oral bioavailability and maximum concentration (Cmax) compared to PX and PX@CD (1:2.5), resulting in improved anti-inflammatory effects in both mouse and rat models. Moreover, PX@CB[7] (1:2.5) had the least adhesion to the gastric mucosa and caused the mildest gastric side effects in rat models when compared to PX, PX@CD (1:2.5), and PX@CB[7] (1:1). Lastly, CB[7] demonstrated good oral biocompatibility in a subacute toxicity evaluation study. These findings indicate that CB[7] could be used as an excipient to improve treatment effectiveness and decrease adverse reactions in orally administered formulations with a favorable safety profile.
Assuntos
Anti-Inflamatórios não Esteroides , Disponibilidade Biológica , Hidrocarbonetos Aromáticos com Pontes , Imidazóis , Piroxicam , Solubilidade , beta-Ciclodextrinas , Animais , Piroxicam/administração & dosagem , Piroxicam/química , Piroxicam/farmacocinética , Piroxicam/efeitos adversos , Imidazóis/química , Imidazóis/administração & dosagem , Imidazóis/farmacocinética , Imidazóis/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/efeitos adversos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/administração & dosagem , Masculino , Camundongos , Ratos Sprague-Dawley , Ratos , Liberação Controlada de Fármacos , Administração Oral , Compostos Heterocíclicos com 2 Anéis , Compostos Macrocíclicos , ImidazolidinasRESUMO
OBJECTIVES: In this research paper, an investigation has been made to assess the simultaneous effect of a solubility enhancement approach, i.e., hydrotropy on the solubility and apparent permeability of piroxicam. The solubility of piroxicam (PRX) a BCS (biopharmaceutics classification system) class II drug has been increased using a mixed hydrotropy approach. This study is based on identifying the pattern of solubility-permeability interplay and confirming whether every solubility gain results in a concomitant decrease in permeability or permeability remains unaffected. METHOD: Solid dispersions of PRX were formulated using two hydrotropes, viz., sodium benzoate (SB) and piperazine (PP) by solvent evaporation method. A comprehensive 32factorial design was employed to study the effect of hydrotropes on the solubility and permeability of PRX. Subsequently, PRX tablets containing these solid dispersions were formulated and evaluated. KEY FINDINGS: SB and PP displayed a significant increase in the solubility of PRX ranging from 0.99 to 2.21 mg/mL for F1-F9 batches attributed to the synergistic effect of hydrotropes. However, there is a reduction in PRX permeability with increasing hydrotrope levels. The decline in permeability was notably less pronounced compared to the simultaneous rise in aqueous solubility of PRX. CONCLUSION: An evident tradeoff between permeability and solubility emerged through the mixed hydrotropic solubilization for PRX. As PRX has generally higher intrinsic permeability, it has been assumed that this permeability loss will not affect the overall absorption of PRX. However, it may affect the absorption of drugs with limited permeability. Therefore, solubility permeability interplay should be investigated during solubility enhancement.
Assuntos
Permeabilidade , Piroxicam , Solubilidade , Piroxicam/química , Química Farmacêutica/métodos , Comprimidos , Excipientes/química , Solventes/químicaRESUMO
This study introduces two innovative nanocarrier systems to improve oral drug delivery. Desosomes and desimicelles combine Deep eutectic solvent (DES) with vesicular or micellar nanosystems, respectively. These novel nanosystems integrate the DES solubilization potency for administering drugs with low aqueous solubility and the vesicular and micellar systems to bypass physiological barriers and improve poor drug bioavailability. Lornoxicam (LRX) is a BCS class II anti-inflammatory with limited aqueous solubility and rapid clearance. Desosomes and desimicelles were prepared and successfully optimized. The optimization depended on particle size, zetapotential, entrapment efficiency, and solubility. The optimized desosomes (LRX-DES-V) and desimicelles (LRX-DES-M) were pictured by transmission electron microscope. Differential scanning calorimetry (DSC) and FTIR analysis indicated the successful inclusion of LRX inside each system. Invitro LRX release profiles revealed controlled release of LRX-DES-V and LRX-DES-M, with more sustained release by the later one. In-vivo study, inflammation was induced using a carrageenan rat model, and the anti-inflammatory effect of LRX-pure, marketed product, traditional niosomes, LRX-DES-V & LRX-DES-M were determined using inhibition %, serum inflammatory cytokines, and histopathology. After 4 h of induction, LRX-DES-M (68.05%) showed a significant inhibition compared to LRX-DES-V (63.57%). LRX-DES-M also showed a better reduction in COX2, PGE2, and TNF-α (1.25-fold, 1.24-fold, and 1.36-fold inhibition), respectively, compared to LRX-DES-V. We can conclude that LRX-DES-V and LRX-DES-M showed better effects than all other groups and that LRX-DES-M might be more effective than LRX-DES-V.
Assuntos
Micelas , Tamanho da Partícula , Piroxicam , Solubilidade , Animais , Ratos , Administração Oral , Piroxicam/administração & dosagem , Piroxicam/farmacocinética , Piroxicam/análogos & derivados , Piroxicam/química , Masculino , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos/química , Disponibilidade Biológica , Liberação Controlada de Fármacos , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Lipossomos , Ratos Wistar , Nanopartículas/química , Solventes/química , Carragenina , Varredura Diferencial de CalorimetriaRESUMO
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 â¼ 465 folds) than commercial LOR due to its increased wettability (contact angle: 74.5° vs 85.6°) and lower solvation free energy (â¼2-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 , ComprimidosRESUMO
The purpose of this study is to investigate the effects of dry and wet mechanochemical synthesis on piroxicam (PX) and saccharin (SA) mixtures. For this purpose, PX and SA mixtures prepared by wet mechanochemical processes using three solvents and by dry mechanochemical synthesis were evaluated by mid-and near-infrared spectroscopy, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The mixtures of wet-type products were transformed into PX/SA 1:1 co-crystals. The effect of the solvent was key to the co-crystallization of PX and SA. The products from the dry process were transformed into the amorphous phase. For the sample of the amorphous mixture, two exothermic peaks due to crystallization were observed in the thermal analysis. Bulk PX was ground for the same number of times for transformation, but was not successfully transformed to the amorphous bulk; the same was observed for SA. It is suggested that the mutual existence of PX and SA promotes mutual amorphization.
Assuntos
Piroxicam , Sacarina , Varredura Diferencial de Calorimetria , Piroxicam/química , Difração de Pó , Pós , Sacarina/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Espectroscopia de Luz Próxima ao Infravermelho , Difração de Raios XRESUMO
SIGNIFICANCE: Statins are an important class of drugs that help to control hyperlipidemia, and one of these statins recently used is pitavastatin calcium (PITA). Nevertheless, the most reported adverse effect of statins is myopathy. Therefore, combining statins with non-steroidal anti-inflammatory drugs (NSAIDs) as Lornoxicam (LORNO) can help in the management of statin-induced myopathy. PURPOSE: This study aimed to formulate and evaluate different oral disintegrating tablets (ODTs) containing PITA using different co-processed excipients. The best PITA-ODT was selected and reformulated with the addition of LORNO, forming a single ODT comprising both drugs. The pharmacokinetic parameters of PITA and LORNO in a single ODT were compared to those of the marketed products (Lipidalon® and Lornoxicam®). METHODS: Eight PITA-ODTs were prepared via direct compression. The prepared PITA-ODTs were evaluated for their weight variation, thickness, breaking force, friability, drug content, and wetting time (WT). In-vitro disintegration time (DT) and dissolution were also evaluated and taken as parameters for selection of the best formula based on the criteria of scoring the fastest DT and highest Q10 min. LORNO was added to the selected PITA-ODT, forming a single ODT (M1) comprising both drugs, which was subjected to an in-vivo pharmacokinetic study using rats as an animal model and liquid chromatography-mass spectrometry (LC-MS/MS) for analysis of both drugs in rat plasma. RESULTS: Results showed that all PITA-ODTs had acceptable physical properties in accordance with pharmacospecial standards. PITA-ODT prepared with Pharmaburst® (F2) had significantly (p<0.05) the fastest DT (6.66±1.52 s) and highest Q10 min (79.07±2.02%) and was chosen as the best formula. The in-vivo pharmacokinetic study of M1 formula showed higher percent relative bioavailability (%RB) of 286.7% and 169.73% for PITA and LORNO, respectively, compared with the marketed products. CONCLUSION: The single ODT comprising PITA and LORNO was promising for instant co-delivery of both drugs with higher %RB when compared with the marketed products.
Assuntos
Sistemas de Liberação de Medicamentos , Piroxicam/análogos & derivados , Quinolinas/administração & dosagem , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Disponibilidade Biológica , Química Farmacêutica/métodos , Cromatografia Líquida , Combinação de Medicamentos , Liberação Controlada de Fármacos , Excipientes/química , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Piroxicam/administração & dosagem , Piroxicam/química , Piroxicam/farmacocinética , Quinolinas/química , Quinolinas/farmacocinética , Ratos , Ratos Wistar , Solubilidade , Comprimidos , Espectrometria de Massas em TandemRESUMO
Meniscus cartilage has poor self-healing capacity in the inner zone and its damage leads to articular cartilage degeneration. Here we have developed hybrid constructs using polycaprolactone (PCL) and polyurethane (PU) surface modified by gelatin (G), chitosan (C), and hyaluronic acid (H) biomacromolecules and piroxicam-loaded gelatin nanofibers (PCL/PU/GCH/P). The surface of constructs was crosslinked using EDC and NHS. The scaffolds were investigated by SEM, FTIR spectroscopy, swelling test, degradation rate, mechanical tests, and in vitro piroxicam release assay. Furthermore, the cell-seeded scaffolds were evaluated by SEM, viability assay, dapi staining, cell migration, proliferation, and gene expression of chondrocytes within these scaffolds. Finally, the animal study was performed in a rabbit model. Chondrocyte and rabbit adipose-derived mesenchymal stem cells (ASCs) from the infrapatellar fat pad (Hoffa's fat pad) were used. Swelling and degradation rate were increased in the modified scaffolds. Tensile and compressive Young's modulus also were near to human native meniscus tissue. The highest expression level of chondrocyte marker genes was observed for the PCL/PU/GCH scaffold. A significant regeneration was obtained in rabbits treated with ASCs-loaded PCL/PU/GCH/P scaffold after 3 months. The surface-modified scaffolds with or without ASCs could successfully accelerate meniscus regeneration and exhibit potential application in meniscus tissue engineering.
Assuntos
Gelatina/química , Piroxicam/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Cartilagem Articular/cirurgia , Menisco/cirurgia , Nanofibras/química , Poliésteres/química , CoelhosRESUMO
Piroxicam (PRX) is a commonly prescribed nonsteroidal anti-inflammatory drug. Its efficacy, however, is partially limited by its low water solubility. In recent years, different studies have tackled this problem and have suggested delivering PRX through solid dispersions. All these strategies, however, involve the use of potentially harmful solvents for the loading procedure. Since piroxicam is soluble in supercritical CO2 (scCO2), the present study aims, for the first time, to adsorb PRX onto mesoporous silica using scCO2, which is known to be a safer and greener technique compared to the organic solvent-based ones. For comparison, PRX is also loaded by adsorption from solution and incipient wetness impregnation using ethanol as solvent. Two different commercial mesoporous silicas are used (SBA-15 and Grace Syloid® XDP), which differ in porosity order and surface silanol population. Physico-chemical analyses show that the most promising results are obtained through scCO2, which yields the amorphization of PRX, whereas some crystallization occurs in the case of adsorption from solution and IWI. The highest loading of PRX by scCO2 is obtained in SBA-15 (15 wt.%), where molecule distribution appears homogeneous, with very limited pore blocking.
Assuntos
Anti-Inflamatórios não Esteroides/química , Inflamação/tratamento farmacológico , Piroxicam/química , Solubilidade/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/uso terapêutico , Etanol/química , Humanos , Piroxicam/uso terapêutico , Dióxido de Silício/química , Água/químicaRESUMO
A nanohybrid formulation of silvertitanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO2/PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/TENO (NT) were loaded onto Ag-TiO2 nanoparticles and coated by PLA via solution casting. The physical interaction between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO2 consists of a cubic phase of Ag with two phases of TiO2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO2/PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO2/PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas Metálicas/química , Norfloxacino/administração & dosagem , Piroxicam/análogos & derivados , Poliésteres/química , Prata/química , Titânio/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Células Hep G2 , Humanos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana/métodos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Norfloxacino/química , Norfloxacino/farmacocinética , Piroxicam/administração & dosagem , Piroxicam/química , Piroxicam/farmacocinética , EspectrofotometriaRESUMO
Detection of the solid-state forms of pharmaceutical compounds is important from the drug performance point of view. Low-frequency Raman (LFR) spectroscopy has been demonstrated to be very sensitive in detecting the different solid-state forms of pharmaceutically relevant compounds. The potential of LFR spectroscopy to probe the in situ isothermal dehydration was studied using piroxicam monohydrate (PXM) and theophylline monohydrate (TPMH) as the model drugs. The dehydration of PXM and TPMH at four different temperatures (95, 100, 105, and 110 °C and 50, 60, 70, and 80 °C, respectively) was monitored in both the low- (20-300 cm-1) and mid-frequency (335-1800 cm-1) regions of the Raman spectra. Principal component analysis and multivariate curve resolution were applied for the analysis of the Raman data. Spectral differences observed in both regions highlighted the formation of specific anhydrous forms of piroxicam and theophylline from their respective monohydrates. The formation of the anhydrous forms was detected on different timescales (approx. 2 min) between the low and mid-frequency Raman regions. This finding highlights the differing nature of the vibrations being detected between these two spectral regions. Computational simulations performed were also in agreement with the experimental results, and allowed elucidating the origin of different spectral features.
Assuntos
Preparações Farmacêuticas/química , Cristalização/métodos , Piroxicam/química , Análise Espectral Raman/métodos , Temperatura , Teofilina/químicaRESUMO
PURPOSE: The goal of this research was to enhance the transdermal delivery of lornoxicam (LX), using nanovesicular carriers composed of the bile salt sodium deoxycholate (SDC), soybean phosphatidyl choline (SPC) and a permeation enhancer limonene. METHODS: Thin-film hydration was the technique employed for the fabrication using a Box-Behnken design with three central points. The investigated factors were SPC molar concentration, SDC amount in mg and limonene percentage (%). The studied responses were percent entrapment efficiency (%EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro drug release (after 2, 10 h). In order to obtain the optimum formula, numerical optimization by Design-Expert® software was used. Electing the optimized bilosomal formula was based on boosting %EE, ZP (as absolute value) and in vitro drug release, taking in consideration diminishing PS and PDI. Further assessment of the selected formula was achieved by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), stability testing, ex vivo skin permeation and deposition. The in vivo pharmacodynamics activities of the optimized formula were examined on male rats and mice and compared to that of the oral market product. RESULTS: The optimized bilosomal formula demonstrated to be nonirritant, with noticeably enhanced anti-inflammatory and antinociceptive activities. Superior in vivo permeation was proved by confocal laser scanning microscopy (CLSM). CONCLUSION: The outcomes demonstrated that bilosomes could improve transdermal delivery of lornoxicam.
Assuntos
Lipossomos/química , Nanoestruturas/química , Piroxicam/análogos & derivados , Administração Cutânea , Animais , Liberação Controlada de Fármacos , Masculino , Camundongos , Tamanho da Partícula , Permeabilidade , Piroxicam/administração & dosagem , Piroxicam/química , Piroxicam/metabolismo , Ratos , Ratos Wistar , Pele/metabolismoRESUMO
BACKGROUND: Piroxicam exhibits low oral bioavailability, due to its meager solubility in water. The intent of this study was to ameliorate the bioavailability of the drug by employing a solubility-enhancing encapsulation technique. METHODS: Seven samples were formulated with piroxicam and gelatin using both solvent evaporation and electrospraying together. Evaluation of solubility and release rate in water and assessment of bioavailability in rats were carried out in comparison with piroxicam plain drug powder (PPDP). Other in vitro explorations were accomplished using powder X-ray diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy. RESULTS: All piroxicam-loaded gelatinnanocontainers (PLGNs) enhanced solubility and release of the payload in water. In particular, a PLGN formulation consisting of piroxicam and gelatin at a 1:8 (w:w) ratio presented about 600-fold the drug solubility of that shown by PPDP. Moreover, 85.12%±10.96% of the payload was released from this formulation in 10 minutes which was significantly higher than that dissolved from PPDP in 10 minutes (11.81%±5.34%). Drug content, drug loading, and encapsulation efficiency of this formulation were 93.41%±0.56%, 10.45%±0.06%, and 66.74%±6.87%, respectively. The drug loaded in PLGNs existed in the amorphous state, as confirmed by X-ray diffraction and differential scanning-calorimetry analyses, and was more stable when analyzed by thermogravimetric analysis. Moreover, Fourier-transform infrared spectroscopy analysis suggested nonexistence of any piroxicam-gelatin interaction in the formulation. In the scanning electron-microscopy image, PLGNs appeared as round, smooth particles, with particle size of <1,000 nm. Amelioration in bioavailability of piroxicam with the aforementioned PLGN formulation was fourfold that of PPDP. CONCLUSION: The PLGN formulation fabricated with piroxicam and gelatin at 1:8 (w:w) might be a promising system for enhanced biopharmaceutical performance of the drug.
Assuntos
Portadores de Fármacos/química , Eletricidade , Gelatina/química , Nanoestruturas/química , Piroxicam/química , Animais , Disponibilidade Biológica , Masculino , Tamanho da Partícula , Piroxicam/farmacocinética , Piroxicam/farmacologia , Ratos , SolubilidadeRESUMO
Aim: To explore the mechanism of gastric carcinogenesis by mining potential hub genes and to search for promising small-molecular compounds for gastric cancer (GC). Materials & methods: The microarray datasets were downloaded from Gene Expression Omnibus database and the genes and compounds were analyzed by bioinformatics-related tools and software. Results: Six hub genes (MKI67, PLK1, COL1A1, TPX2, COL1A2 and SPP1) related to the prognosis of GC were confirmed to be upregulated in GC and their high expression was correlated with poor overall survival rate in GC patients. In addition, eight candidate compounds with potential anti-GC activity were identified, among which resveratrol was closely correlated with six hub genes. Conclusion: Six hub genes identified in the present study may contribute to a more comprehensive understanding of the mechanism of gastric carcinogenesis and the predicted potential of resveratrol may provide valuable clues for the future development of targeted anti-GC inhibitors.
Assuntos
Perfilação da Expressão Gênica , Genes Neoplásicos , Proteínas de Neoplasias/genética , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Amiodarona/química , Proteínas de Ciclo Celular/genética , Clomipramina/química , Colágeno Tipo I/genética , Bases de Dados Genéticas , Conjuntos de Dados como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Levalorfano/química , Proteínas Associadas aos Microtúbulos/genética , Osteopontina/genética , Piroxicam/química , Procaína/química , Procaína/farmacologia , Procaína/uso terapêutico , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Resveratrol/química , Resveratrol/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Ácido Ursodesoxicólico/química , Vorinostat/química , Quinase 1 Polo-LikeRESUMO
Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs) can solubilize hydrophobic drugs in water enhancing their bioavailability. In this theoretical study based on molecular mechanics and molecular dynamics methods, the interactions between ß-cyclodextrin and piroxicam, an important nonsteroidal anti-inflammatory drug, were investigated. At first, both host-guest complexes with native ß-CD in the 1:1 and in 2:1 stoichiometry were considered without assuming any initial a priori inclusion: the resulting inclusion complexes were in good agreement with literature NMR data. The interaction between piroxicam and a ß-CD nanosponge (NS) was then modeled at different concentrations. Two inclusion mechanisms were found. Moreover, piroxicam can interact with the external NS surface or with its crosslinkers, also forming one nanopore. At larger concentration, a nucleation process of drug aggregation induced by the first layer of adsorbed piroxicam molecules is observed. The flexibility of crosslinked ß-CDs, which may be swollen or quite compact, changing the surface area accessible to drug molecules, and the dimension of the aggregate nucleated on the NS surface are important factors possibly affecting the kinetics of release, which shall be theoretically studied in more detail at specific concentrations.
Assuntos
Anti-Inflamatórios não Esteroides/química , Portadores de Fármacos/química , Simulação de Dinâmica Molecular , Piroxicam/química , beta-Ciclodextrinas/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e HidrofílicasRESUMO
In the present work, tenoxicam (H2Ten) reacted with Mn(II), Co(II), Ni(II), Cu(II) and Zn (II) ions in the presence of 1.10-phenthroline (Phen), forming new mixed ligand metal complexes. The properties of the formed complexes were depicted by elemental analyses, infrared, electronic spectra, proton nuclear magnetic resonance (1H NMR), mass spectrometry, thermogravimetric (TGA) and differential thermogravimetric (DTG) analysis, molar conductance and magnetic moment. IR spectra demonstrated that H2Ten acted as a neutral bidentate ligand, coordinated to the metal ions via the pyridine-N and carbonyl group of the amide moiety, and Phen through the nitrogen atoms. Kinetic thermodynamics parameters activation energy (E*), enthalpy of activation (ΔH*), entropy of activation (ΔS*), Gibbs, free energy (ΔG*) associated to the complexes have been evaluated. Antibacterial screening of the compounds was carried out in vitro against Clavibacter michiganensis, Xanthomonas campestris and Bacillus megaterium. Antifungal activity was performed in vitro against Monilinia fructicola, Penicillium digitatum and Colletotrichum acutatum. The possible phytotoxic effect of the studied compounds was also investigated on Solanum lycopersicum (tomatoes) and Lepidium sativum (garden cress) seeds. The anticancer activity was screened against cell cultures of HCT-116 (human colorectal carcinoma), HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma).
Assuntos
Antibacterianos/química , Antifúngicos/química , Complexos de Coordenação/química , Piroxicam/análogos & derivados , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bacillus megaterium/efeitos dos fármacos , Cobalto/química , Complexos de Coordenação/farmacologia , Cobre/química , Humanos , Ligantes , Espectroscopia de Ressonância Magnética , Manganês/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Níquel/química , Piroxicam/química , Piroxicam/farmacologia , Bases de Schiff , Espectrofotometria Infravermelho , Termodinâmica , Xanthomonas campestris/efeitos dos fármacos , Zinco/químicaRESUMO
Covalent triazine-based polymers (CTPs) are a new class of porous materials that can be used for the intercalation of therapeutic agents. The main purposes of designing new drug carriers include protecting them from degradation, enhancing their poor aqueous solubility, and investigating their controlled release properties. In this context, a novel polybenzimidazole-based CTP (BZ-CTP) was prepared by a solvothermal reaction between 4,4',4â³-((1,3,5-triazine-2,4,6-triyl) tris(azanediyl)) tribenzoic acid (TCA) and 3,3'-diaminobenzidine. Piroxicam (PRX) and mefenamic acid (MFA) were loaded thoroughly into the CTP by using ultrasonication to form MFA-loaded CTP (MFA@BZ-CTP) and PRX-loaded CTP (PRX@BZ-CTP) with drug loading efficiencies of 49% and 53%, respectively. We attribute the increased loading efficiencies to the formation of π-π stacking forces between the aromatic rings present in the CTP structure and drugs. The in vitro release experiments were assessed in simulated physiological conditions using the dialysis method. Moreover, the release mechanisms were evaluated by Korsmeyer-Peppas kinetic studies and the obtained results showed excellent sustained releases of 81% after 96 h and 87% after 24 h for the PRX@BZ-CTP and MFA@BZ-CTP hybrids, respectively.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Benzimidazóis/química , Portadores de Fármacos/química , Polímeros/química , Triazinas/química , Dióxido de Carbono , Cinética , Ácido Mefenâmico/química , Nanopartículas/química , Piroxicam/química , Porosidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios XRESUMO
This study demonstrates, for the first time, the ability of surface-enhanced Raman chemical imaging (SER-CI) combined with multivariate analysis to detect low levels (0.1% (w/w)) of a polymorphic form in a pharmaceutical mixture. In the studied formulation, piroxicam was used as a model molecule to develop this approach. Piroxicam is a widely available non-steroidal anti-inflammatory drug, exhibiting an interesting case of polymorphism, with two most commonly observed forms (ß and α2). In this work, the SERS spectra of piroxicam polymorphic forms ß and α2 are presented. These forms showed clear spectral differences in terms of band position and intensity. From a crystallographic point of view, the difference of exaltation between both forms was correlated with a preferred orientation of crystallites of form α2 making its SERS detection difficult compared to form ß. A preferred orientation of the (1k0) crystallographic planes of α2 was demonstrated in samples, not promoting an appropriate molecular orientation onto the metallic surface. Additionally, a semi-quantitative approach using SER-CI combined with chemometric tools was developed enabling to detect crystallites of form ß below the detection limit of conventional Raman microscopy. The exaltation of the Raman signal in the presence of silver nanoparticles allowed a higher sensitivity and a reduction of the acquisition time by a factor of 6.
Assuntos
Piroxicam/química , Comprimidos/química , Anti-Inflamatórios não Esteroides/química , Química Farmacêutica/métodos , Nanopartículas Metálicas/química , Análise Multivariada , Prata/química , Análise Espectral Raman/métodosRESUMO
The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, molecular docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC analysis indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and molecular docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% respectively indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 months showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.