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1.
Inflammopharmacology ; 29(6): 1719-1731, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34550498

ABSTRACT

Aim of this study was to evaluate and compare the efficacy of anti-arthritic drugs (naproxen, prednisolone, and hydroxychloroquine) alone and in combination. The in vitro anti-arthritic activity was evaluated by stabilization of human erythrocytes (HRBCs) membrane assays. In vivo activity was carried out using Complete Freund's Adjuvant (CFA) induced arthritic model in Wistar rat. Individual and combination drugs were administered for 21 days in rats 8 days post inoculation with CFA (0.15 ml injected in right hind paw). Body weight and paw edema were measured at different intervals. Combination treatments exhibited more HRBC stabilization than individual treatments. All individual and combination treatments reduced the level of C-reactive protein (CRP), liver function enzymes, malondialdehyde, white blood cells and platelets, with the most pronounced activity exhibited by the combination of three drugs. The level of oxidative stress biomarkers (reduced glutathione, catalase, and superoxide dismutase), red blood cells, and hemoglobin were notably increased in all treatment groups in contrasts to diseased control rats. Histopathological evaluation of the paw showed that all the treatments had reduced (p < 0.05-0.001) the arthritic indices in contrasts to diseased control rats. The serum concentrations of TNF-α and PGE2 were provoked in diseased control rats but had been notably (p < 0.0001) restored by treatments with individual and combination drugs. It was also found that combination treatments, more precisely triple drug was remarkably effective in treating arthritis. It can be concluded that naproxen, prednisolone, and hydroxychloroquine effectively ameliorated the CFA-induced arthritis and were more effective in combination as compared to individual drug therapy probably due to reduction in oxidative stress and inflammatory markers. Moreover, two lower doses (half NPH/2 and one-third NPH/3) of triple combination therapy naproxen, prednisolone, and hydroxychloroquine (NPH) showed no significant difference in anti-arthritic effect as compared to the highest dose level of NPH.


Subject(s)
Arthritis, Experimental/drug therapy , Hydroxychloroquine/pharmacology , Naproxen/pharmacology , Prednisolone/pharmacology , Animals , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/pharmacology , Arthritis, Experimental/pathology , Erythrocytes/drug effects , Erythrocytes/metabolism , Female , Freund's Adjuvant , Humans , Hydroxychloroquine/administration & dosage , Inflammation/drug therapy , Inflammation/pathology , Male , Naproxen/administration & dosage , Oxidative Stress/drug effects , Prednisolone/administration & dosage , Rats , Rats, Wistar
2.
Drug Des Devel Ther ; 15: 3675-3683, 2021.
Article in English | MEDLINE | ID: mdl-34465979

ABSTRACT

BACKGROUND AND OBJECTIVE: Bioequivalence tests are fundamental step in assessing the equivalence in bioavailability between a test and reference product. In practice, two separate linear mixed models (LMMs) with random subject effects, which have an area under the concentration-time curve (AUC) and the peak concentration (Cmax) as the responses, have become the gold standard for evaluating bioequivalence. Recently, Lee et al developed a multivariate hierarchical generalized linear model (HGLM) for several responses that modeled correlations among multivariate responses via correlated random effects. The objective of this study was to apply this multivariate analysis to the bioequivalence test in practice and to compare the performance of multivariate HGLM and separate LMMs. METHODS: Three pharmacokinetic datasets, fixed-dose combination (naproxen and esomeprazole), tramadol and fimasartan data were analyzed. We compared the 90% confidence interval (CI) for the geometric mean ratio (GMR) of a test product to a reference product using the multivariate HGLM and two conventional separate LMMs. RESULTS: We found that the 90% CIs for the GMRs of both AUC and Cmax from the multivariate HGLM were narrower than those from the separate LMMs: (0.843, 1.152) vs (0.825, 1.177) for Cmax of esomeprazole in fixed-dose combination data; (0.805, 0.931) vs (0.797, 0.941) for Cmax in tramadol data; (0.801, 1.501) vs (0.762, 1.578) for Cmax and (1.163, 1.332) vs (1.009, 1.341) for AUC in fimasartan data, consistent with the random subject effects from two separate LMMs being highly correlated in the three datasets (correlation coefficient r = 0.883; r = 0.966; r = 0.832). CONCLUSION: This multivariate HGLM had good performance in the bioequivalence test with multiple endpoints. This method would provide a more reasonable option to reduce the 90% CI by adding correlation parameters and thus an advantage especially in evaluating the bioequivalence of highly variable drugs with broad 90% CIs.


Subject(s)
Biphenyl Compounds/pharmacokinetics , Esomeprazole/pharmacokinetics , Models, Statistical , Pyrimidines/pharmacokinetics , Tetrazoles/pharmacokinetics , Tramadol/pharmacokinetics , Area Under Curve , Biological Availability , Biphenyl Compounds/administration & dosage , Datasets as Topic , Drug Combinations , Esomeprazole/administration & dosage , Humans , Linear Models , Male , Multivariate Analysis , Naproxen/administration & dosage , Naproxen/pharmacokinetics , Pyrimidines/administration & dosage , Randomized Controlled Trials as Topic , Tetrazoles/administration & dosage , Therapeutic Equivalency , Tramadol/administration & dosage
3.
Biomolecules ; 11(12)2021 12 18.
Article in English | MEDLINE | ID: mdl-34944543

ABSTRACT

Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.


Subject(s)
Drug Discovery , Gasotransmitters/pharmacology , Hydrogen Sulfide/pharmacology , Animals , Benzenesulfonates/administration & dosage , Benzenesulfonates/metabolism , Benzenesulfonates/pharmacology , Benzenesulfonates/therapeutic use , Chemistry, Pharmaceutical , Gasotransmitters/administration & dosage , Gasotransmitters/metabolism , Gasotransmitters/therapeutic use , Humans , Hydrogen Sulfide/administration & dosage , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/therapeutic use , Morpholines/administration & dosage , Morpholines/metabolism , Morpholines/pharmacology , Morpholines/therapeutic use , Naproxen/administration & dosage , Naproxen/analogs & derivatives , Naproxen/metabolism , Naproxen/pharmacology , Naproxen/therapeutic use , Organothiophosphorus Compounds/administration & dosage , Organothiophosphorus Compounds/metabolism , Organothiophosphorus Compounds/pharmacology , Organothiophosphorus Compounds/therapeutic use
4.
Sci Rep ; 11(1): 20191, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642409

ABSTRACT

A drug delivery system based on mesoporous particles MCM-41 was post-synthetically modified by photo-sensitive ligand, methyl-(2E)-3-(4-(triethoxysilyl)-propoxyphenyl)-2-propenoate (CA) and the pores of MCM-41 particles were loaded with Naproxen sodium salt (NAP). The CA was used as a photoactive molecule that can undergo a reversible photo-dimerization by [2π + 2π] cycloaddition when irradiated with UV light of specific wavelengths. Thus, it has a function of gate-keeper that is responsible for opening/closing the pores and minimizing premature release of NAP. The physicochemical properties of the prepared system were studied by infrared spectroscopy (IR), nitrogen adsorption measurements, thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDX). The mechanism of the opening/closing pores was confirmed by UV measurements. In vitro and in vivo drug release experiments and the concentration of released NAP was determined by UV spectroscopy and high-performance liquid chromatography (HPLC). In vivo drug release in the blood circulatory system of rats has demonstrated the effective photo-cleavage reaction of CA molecules after UV-light stimulation. The localization and morphological changes of the particles were studied in the blood and liver of rats at different time intervals. The particles in the blood have been shown to retain their original rod-like shape, and the particles in the liver have been hydrolysed, which has resulted in spherical shape with a reduced size.


Subject(s)
Drug Carriers/chemistry , Naproxen , Silicon Dioxide/chemistry , Animals , Drug Liberation , Male , Naproxen/administration & dosage , Naproxen/pharmacokinetics , Rats , Rats, Wistar , Solubility
5.
Dalton Trans ; 50(29): 10275-10290, 2021 Jul 27.
Article in English | MEDLINE | ID: mdl-34254077

ABSTRACT

Layered rare-earth hydroxides have begun to gather increasing attention as potential theranostic platforms owing to their extensive intercalation chemistry combined with magnetic and fluorescent properties. In this work, the potential of layered terbium hydroxide (LTbH) as a platform for simultaneous drug delivery and fluorescence imaging was evaluated. LTbH-Cl ([Tb2(OH)5]Cl·yH2O) was loaded with three nonsteroidal anti-inflammatory drugs (diclofenac, ibuprofen, and naproxen) via ion-exchange. Drug release studies in phosphate buffered saline (pH = 7.4) revealed all three formulations release their drug cargo rapidly over the course of approximately 5 hours. In addition, solid state fluorescence studies indicated that fluorescence intensity is strongly dependent on the identity of the guest anion. It was postulated that this feature may be used to track the extent of drug release from the formulation, which was subsequently successfully demonstrated for the ibuprofen loaded LTbH. Overall, LTbH exhibits good biocompatibility, high drug loading, and a strong, guest-dependent fluorescence signal, all of which are desirable qualities for theranostic applications.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Diclofenac/administration & dosage , Drug Delivery Systems , Hydroxides/administration & dosage , Ibuprofen/administration & dosage , Naproxen/administration & dosage , Terbium/administration & dosage , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Caco-2 Cells , Cell Survival/drug effects , Diclofenac/chemistry , Drug Liberation , Drug Stability , Erythrocytes/drug effects , Female , HEK293 Cells , Hemolysis/drug effects , Humans , Hydroxides/chemistry , Ibuprofen/chemistry , Ion Exchange , Naproxen/chemistry , Optical Imaging , Rats, Wistar , Terbium/chemistry
6.
AAPS PharmSciTech ; 22(3): 85, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33650023

ABSTRACT

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.


Subject(s)
Drug Compounding/methods , Naproxen/administration & dosage , Naproxen/chemical synthesis , Technology, Pharmaceutical/methods , Administration, Oral , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Dosage Forms , Drug Liberation , Excipients/administration & dosage , Excipients/chemical synthesis , Excipients/pharmacokinetics , Naproxen/pharmacokinetics , Tablets
7.
Drug Metab Dispos ; 49(5): 345-352, 2021 05.
Article in English | MEDLINE | ID: mdl-33632714

ABSTRACT

Alaska Native people are under-represented in genetic research but have unique gene variation that may critically impact their response to pharmacotherapy. Full resequencing of CYP2C9 in a cross-section of this population identified CYP2C9 Met1Leu (M1L), a novel, relatively common single nucleotide polymorphism hypothesized to confer CYP2C9 poor metabolizer phenotype by disrupting the start codon. M1L is present at a minor allele frequency of 6.3% in Yup'ik Alaska Native people and thus can contribute to the risk of an adverse drug response from narrow-therapeutic-index CYP2C9 substrates such as (S)-warfarin. This study's objective was to characterize the catalytic efficiency of the Leu1 variant enzyme in vivo by evaluating the pharmacokinetic behavior of naproxen, a probe substrate for CYP2C9 activity, in genotyped Yup'ik participants. We first confirmed the selectivity of (S)-naproxen O-demethylation by CYP2C9 using activity-phenotyped human liver microsomes and selective cytochrome P450 inhibitors and then developed and validated a novel liquid chromatography mass spectrometry method for simultaneous quantification of (S)-naproxen, (S)-O-desmethylnaproxen, and naproxen acyl glucuronide in human urine. The average ratio of (S)-O-desmethylnaproxen to unchanged (S)-naproxen in urine was 18.0 ± 8.0 (n = 11) for the homozygous CYP2C9 Met1 reference group and 10.3 ± 6.6 (n = 11) for the Leu1 variant carrier group (P = 0.011). The effect of M1L variation on CYP2C9 function and its potential to alter the pharmacokinetics of drugs metabolized by the enzyme has clinical implications and should be included in a variant screening panel when pharmacogenetic testing in the Alaska Native population is warranted. SIGNIFICANCE STATEMENT: The novel CYP2C9 Met1Leu variant in Alaska Native people was recently identified. This study validated (S)-naproxen as a CYP2C9 probe substrate to characterize the in vivo functional activity of the CYP2C9 Leu1 variant. The results of this pharmacogenetic-pharmacokinetic study suggest that the CYP2C9 Leu1 variant exhibits loss of enzyme activity. This finding may be important to consider when administering narrow-therapeutic-index medications metabolized by CYP2C9 and also compels further investigation to characterize novel genetic variation in understudied populations.


Subject(s)
Alaskan Natives/genetics , Anti-Inflammatory Agents, Non-Steroidal/urine , Cytochrome P-450 CYP2C9/genetics , Cytochrome P-450 CYP2C9/metabolism , Genetic Variation/genetics , Naproxen/urine , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cross-Sectional Studies , Female , Humans , Leucine/genetics , Male , Methionine/genetics , Naproxen/administration & dosage , Young Adult
8.
Pharm Dev Technol ; 26(5): 509-521, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33593203

ABSTRACT

In this study, the aerogel technology was used to prepare pulmonary drug carriers consisting of alginate and alginate-hyaluronic acid by an emulsion gelation technique and supercritical CO2 drying. During the preparation process, the emulsification rate and inner phase viscosity were varied to control the diameter of aerogel microspheres. Results showed that the aerogel microspheres were highly porous (porosity > 98%) with low densities in the range between 0.0087 and 0.0634 g/cm3 as well as high surface areas between 354 and 759 m2/g. The obtained microspheres showed aerodynamic diameter below 5 µm making them suitable for pulmonary drug delivery. An in vitro drug release study with the model drug sodium naproxen was conducted and a non-Fickian drug release mechanism was observed, with no significant difference between the release profiles of alginate and alginate-hyaluronic acid microspheres. During the emulsion gelation step, the feasibility of using the capillary number to estimate the largest stable droplet size in the emulsions was also studied and it was found that using this number, the droplet size in the emulsions may well be predicted.


Subject(s)
Alginates/chemistry , Drug Delivery Systems , Hyaluronic Acid/chemistry , Naproxen/administration & dosage , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Drug Liberation , Emulsions , Gels , Lung/metabolism , Microspheres , Naproxen/pharmacokinetics , Particle Size , Porosity , Technology, Pharmaceutical , Tissue Distribution , Viscosity
9.
Mol Pharm ; 18(3): 1157-1166, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33504154

ABSTRACT

Though pharmaceutical polymers were widely used in inhibiting drug recrystallization via strong intermolecular hydrogen and ionic bonds, the improved drug stability was achieved at the cost of the drug release rate or amount in the drug-in-adhesive transdermal patch. To overcame the difficulty, this study aimed to increase drug loading utilizing a novel drug-ionic liquid (drug-IL) strategy and illustrate the underlying molecular mechanism. Here, naproxen (NPX) and triamylamine (TAA) were chosen as the model drug and corresponding counterion, respectively. In addiiton, carboxylic pressure-sensitive adhesive (PSA) was chosen as the model polymer. The drug-IL (NPX-TAA) was synthesized and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and proton nuclear magnetic resonance. The miscibility between NPX-TAA and PSA was assessed using microscopy study, X-ray diffraction, fluorescence spectroscopy, and solubility parameter calculation. In addition, molecular mechanisms of crystallization inhibition were revealed by FT-IR, Raman spectroscopy, DSC, X-ray photoelectron spectroscopy (XPS), and molecular docking. Finally, the release pattern of the high load patch of NPX-TAA was evaluated using in vitro drug release and verified by a skin permeation experiment. The results showed that drug loading in PSA was increased by 5.0 times, which was caused by the synergistic effect of strong ionic hydrogen bonding (the decreased intensity and blue shift of the O-H peak of COOH in PSA) formed between NPX-TAA and PSA-COO- and normal hydrogen bonding (red shift of the C═O peak in PSA) formed between NPX-TAA and the carbonyl group of PSA. In addition, -NH+ of TAA was confirmed as the molecular basis of ionic hydrogen bonding through new peak appearance (binding energy: 400.0 eV) in XPS spectra. Moreover, high drug release percent (80.8 ± 1.8%) was achieved even at high drug loading compared with the control group (72.4 ± 2.2%). Thus, this study introduced an effective drug-IL method to enhance drug loading capacity and illustrated the brand-new action mechanism, which provided a powerful instrument for the development of a high drug loading-high release patch.


Subject(s)
Adhesives/chemistry , Hydrogen/chemistry , Ionic Liquids/chemistry , Macrocyclic Compounds/chemistry , Adhesives/administration & dosage , Animals , Calorimetry, Differential Scanning/methods , Crystallization/methods , Drug Liberation/drug effects , Hydrogen Bonding/drug effects , Macrocyclic Compounds/administration & dosage , Molecular Docking Simulation/methods , Naproxen/administration & dosage , Naproxen/chemistry , Photoelectron Spectroscopy/methods , Polymers/chemistry , Rabbits , Skin/drug effects , Skin Absorption/drug effects , Solubility/drug effects , Spectroscopy, Fourier Transform Infrared/methods , Spectrum Analysis, Raman/methods , Transdermal Patch , X-Ray Diffraction/methods
10.
Pharm Dev Technol ; 26(2): 193-208, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33211618

ABSTRACT

In this work, the tabletability and dissolution of spray-dried forms of naproxen and its sodium salt were compared with those of unprocessed drugs. Solutions of naproxen or naproxen sodium alone or with HPMC (5% w/w of drug content) were spray dried. Scanning electron micrographs showed that naproxen sodium spray-dried particles were spherical, whereas those of naproxen were non-spherical but isodiametric. Powder x-ray diffraction and thermal analysis indicated that co-spray drying with HPMC resulted in reduced crystallinity of naproxen and higher naproxen sodium dihydrate content. FTIR and Raman analysis showed shifting, merging or elimination of bands in the spectra of the co-spray dried products signifying solid-state alterations. When mixed with suitable processing aids (7% w/w), all co-spray dried powders produced satisfactory tablets in the pressure range 73-295 MPa. Conversely, physical mixtures of naproxen compressed with the same aids failed tableting, whereas naproxen sodium produced weak tablets. Dissolution tests showed significant improvement for co-spray dried drugs tablets. Therefore, since the large therapeutic doses of naproxen and sodium naproxen limit the use of tableting aids, the improved compaction and dissolution performance of the spray-dried forms may be a formulation alternative.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Chemistry, Pharmaceutical , Hypromellose Derivatives/chemistry , Naproxen/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Crystallization , Drug Compounding/methods , Drug Liberation , Excipients/chemistry , Naproxen/chemistry , Solubility , Spray Drying , Tablets
11.
PLoS One ; 15(8): e0236297, 2020.
Article in English | MEDLINE | ID: mdl-32780750

ABSTRACT

Naproxen is a widely used non-steroidal anti-inflammatory drug for the control of postoperative inflammatory signs and symptoms in dentistry. Its association with esomeprazole has been widely studied and has yielded good results for the control of acute pain, even with the delayed absorption of naproxen owing to the presence of esomeprazole. To further understand the absorption, distribution, and metabolism of this drug alone and in combination with esomeprazole, we will analyze the pharmacokinetic parameters of naproxen and its major metabolite, 6-O-desmethylnaproxen, in saliva samples. A rapid, sensitive, and selective liquid chromatography-tandem mass spectrometric method for the simultaneous determination of naproxen and 6-O-desmethylnaproxen in saliva will be developed and validated. Sequential saliva samples from six patients will be analyzed before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6 8, 11, 24, 48, 72, and 96 h after the ingestion of one naproxen tablet (500 mg) and esomeprazole-associated naproxen tablets (500 + 20 mg), at two different times. After liquid-liquid extraction with ethyl acetate and HCl, the samples will be analyzed using an 8040 Triple Quadrupole Mass Spectrometer (Shimadzu, Kyoto, Japan). Separation of naproxen and its major metabolic products will be performed using a Shim-Pack XR-ODS 75Lx2.0 column and C18 pre-column (Shimadzu, Kyoto, Japan) at 40°C using a mixture of methanol and 10 mM ammonium acetate (70:30, v/v) with an injection flow of 0.3 mL/min. The total analytical run time will be 5 min. The detection and quantification of naproxen and its metabolite will be validated, which elucidate the pharmacokinetics of this drug, thereby contributing to its proper prescription for the medical and dental interventions that cause acute pain.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Drug Monitoring/methods , Esomeprazole/pharmacokinetics , Naproxen/analogs & derivatives , Saliva/chemistry , Administration, Oral , Adolescent , Adult , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Chromatography, High Pressure Liquid/methods , Dose-Response Relationship, Drug , Drug Combinations , Esomeprazole/administration & dosage , Esomeprazole/isolation & purification , Female , Gastrointestinal Absorption , Humans , Male , Methanol/chemistry , Middle Aged , Naproxen/administration & dosage , Naproxen/isolation & purification , Naproxen/pharmacokinetics , Pain, Procedural/drug therapy , Reproducibility of Results , Tablets , Tandem Mass Spectrometry/methods , Young Adult
12.
Actual. osteol ; 15(3): 225-236, Sept-Dic. 2019. ilus
Article in English | LILACS (Americas) | ID: biblio-1116171

ABSTRACT

Bone grafting is important to preserve the alveolar bone ridge height and volume for dental implant placement. Even though implant-supported overdentures present highly successful outcomes, it seems that a great number of edentulous individuals have not pursued implant-based rehabilitation. The cost of the treatment is one of the reasons of discrepancy between highly successful therapy and its acceptance. Therefore, the development of biomaterials for bone grafting with comparable characteristics and biological effects than those renowned internationally, is necessary. In addition, domestic manufacture would reduce the high costs in public health arising from the application of these biomaterials in the dental feld. The purpose of this clinical case report is to provide preliminary clinical evidence of the efficacy of a new bovine bone graft in the bone healing process when used for sinus floor elevation. (AU)


El uso de injertos óseos es importante para preservar la altura y el volumen de la cresta alveolar para la colocación de implantes dentales. Si bien las sobredentaduras implanto-soportadas presentan resultados altamente exitosos, la mayoría de las personas desdentadas no han sido rehabilitadas mediante implantes dentales. Uno de los principales motivos por los cuales los pacientes no aceptan este tipo de tratamiento, altamente exitoso, es el elevado costo del mismo. Por ello, es necesario el desarrollo de biomateriales de injerto óseo con características y efectos biológicos comparables a los reconocidos internacionalmente. Asimismo, la fabricación nacional reduciría los altos costos en Salud Pública derivados de la aplicación de estos biomateriales en el campo dental. El objetivo de esta comunicación es presentar un caso clínico a fin de proporcionar evidencia preliminar acerca de la eficacia de un nuevo injerto de hueso bovino en el proceso de cicatrización ósea en el levantamiento del piso del seno maxilar. (AU)


Subject(s)
Humans , Animals , Female , Middle Aged , Cattle , Rats , Bone Transplantation/methods , Jaw, Edentulous, Partially/rehabilitation , Sinus Floor Augmentation/methods , Osteogenesis , Argentina , Biocompatible Materials , Cattle/physiology , Carticaine/administration & dosage , Chlorhexidine/administration & dosage , Naproxen/administration & dosage , Public Health/economics , Osseointegration , Dentures , Bone Transplantation/trends , Jaw, Edentulous, Partially/pathology , Jaw, Edentulous, Partially/therapy , Durapatite/therapeutic use , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Dental Implantation, Endosseous/methods , Sinus Floor Augmentation/trends , Allografts/immunology , Allografts/transplantation
13.
Curr Drug Deliv ; 17(10): 885-897, 2020.
Article in English | MEDLINE | ID: mdl-32713340

ABSTRACT

BACKGROUND: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis. OBJECTIVE: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model. METHODS: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies. RESULTS: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9µm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9µm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel. CONCLUSION: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.


Subject(s)
Arthritis , Naproxen/administration & dosage , Skin Absorption , Administration, Cutaneous , Animals , Arthritis/drug therapy , Drug Carriers , Liposomes , Nanoparticles , Particle Size , Rats , Skin/metabolism
14.
Meet. odontol ; 1(4): 18-23, 2000. ilus, tab
Article in Spanish | LIPECS | ID: biblio-1109395

ABSTRACT

Se comparó la eficacia analgésica y la duración de la acción de naproxeno sódico, administrado en una dosis de 440 mg (n = 92), acetaminofén, en una dosis de 1000 mg (n = 89) y placebo (n = 45) en un estudio con dosis únicas, randomizado, a doble ciego y de 12 horas de duración, en pacientes con dolor por lo menos moderado, secundario a la extracción de tres o cuatro piezas molares de tercer orden. El tiempo hasta medicarse nuevamente, una medida de la duración del efecto analgésico, fue significativamente mayor (P < 0.001) con naproxeno sódico (mediante, 9.9 horas) en comparación con acetaminofén (mediante, 3.1 horas) o placebo (mediana, 2.0 horas). Naproxeno sódico también fue superior a acetaminofén en la diferencia de la intensidad máxima (pico) del dolor (escala análoga visual), en la sumatoria de las diferencias de la intensidad del dolor, en el alivio máximo del dolor, en el tiempo para disminuir el dolor en un 50 por ciento; y en la calificación total. Los porcentajes totales de pacientes que reportaron eventos adversos; y los tipos de eventos reportados, fueron comparables con los tres tratamientos. Por tanto, naproxeno sódico demostró una superior eficacia y tolerabilidad similar a acetaminofén en el presente modelo de dolor dental postoperatorio.


Subject(s)
Male , Female , Child , Adolescent , Adult , Humans , Acetaminophen/administration & dosage , Acetaminophen/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Naproxen/administration & dosage , Naproxen/analysis , Naproxen/pharmacology
15.
Gut ; 70(3): 555-566, 2021 03.
Article in English | MEDLINE | ID: mdl-32641470

ABSTRACT

OBJECTIVE: Patients with Lynch syndrome (LS) are at markedly increased risk for colorectal cancer. It is being increasingly recognised that the immune system plays an essential role in LS tumour development, thus making an ideal target for cancer prevention. Our objective was to evaluate the safety, assess the activity and discover novel molecular pathways involved in the activity of naproxen as primary and secondary chemoprevention in patients with LS. DESIGN: We conducted a Phase Ib, placebo-controlled, randomised clinical trial of two dose levels of naproxen sodium (440 and 220 mg) administered daily for 6 months to 80 participants with LS, and a co-clinical trial using a genetically engineered mouse model of LS and patient-derived organoids (PDOs). RESULTS: Overall, the total number of adverse events was not different across treatment arms with excellent tolerance of the intervention. The level of prostaglandin E2 in the colorectal mucosa was significantly decreased after treatment with naproxen when compared with placebo. Naproxen activated different resident immune cell types without any increase in lymphoid cellularity, and changed the expression patterns of the intestinal crypt towards epithelial differentiation and stem cell regulation. Naproxen demonstrated robust chemopreventive activity in a mouse co-clinical trial and gene expression profiles induced by naproxen in humans showed perfect discrimination of mice specimens with LS and PDOs treated with naproxen and control. CONCLUSIONS: Naproxen is a promising strategy for immune interception in LS. We have discovered naproxen-induced gene expression profiles for their potential use as predictive biomarkers of drug activity. TRIAL REGISTRATION NUMBER: gov Identifier: NCT02052908.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chemoprevention , Colorectal Neoplasms, Hereditary Nonpolyposis/drug therapy , Colorectal Neoplasms, Hereditary Nonpolyposis/immunology , Naproxen/pharmacology , Adult , Aged , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Dinoprostone/metabolism , Disease Models, Animal , Female , Humans , Intestinal Mucosa/metabolism , Male , Mice , Middle Aged , Naproxen/administration & dosage
16.
Daru ; 28(2): 507-516, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32562159

ABSTRACT

BACKGROUND: There is no identified pharmacological therapy for COVID-19 patients, where potential therapeutic strategies are underway to determine effective therapy under such unprecedented pandemic. Therefore, combination therapies may have the potential of alleviating the patient's outcome. This study aimed at comparing the efficacy of two different combination regimens in improving outcomes of patients infected by novel coronavirus (COVID-19). METHODS: This is a single centered, retrospective, observational study of 60 laboratory-confirmed COVID-19 positive inpatients (≥18 years old) at two wards of the Baqiyatallah Hospital, Tehran, Iran. Patient's data including clinical and laboratory parameters were recorded. According to the drug regimen, the patients were divided into two groups; group I who received regimen I consisting azithromycin, prednisolone, naproxen, and lopinavir/ritonavir and group II who received regimen II including meropenem, levofloxacin, vancomycin, hydroxychloroquine, and oseltamivir. RESULTS: The oxygen saturation (SpO2) and temperature were positively changed in patients receiving regimen I compared to regimen II (P = 0.013 and P = 0.012, respectively). The serum level of C-reactive protein (CRP) changed positively in group I (P < 0.001). Although there was a significant difference in platelets between both groups (75.44 vs 51.62, P < 0.001), their change did not clinically differ between two groups. The findings indicated a significant difference of the average length of stay in hospitals (ALOS) between two groups, where the patients under regimen I showed a shorter ALOS (6.97 vs 9.93, P = 0.001). CONCLUSION: This study revealed the beneficial effect of the short-term use of low-dose prednisolone in combination with azithromycin, naproxen and lopinavir/ritonavir (regimen I), in decreasing ALOS compared to regimen II. Since there is still lack of evidence for safety of this regimen, further investigation in our ongoing follow-up to deal with COVID-19 pneumonia is underway. Graphical abstract.


Subject(s)
Hospitalization/statistics & numerical data , Pneumonia, Viral/drug therapy , Adult , Aged , Azithromycin/administration & dosage , COVID-19/complications , Drug Combinations , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Iran , Length of Stay , Levofloxacin/administration & dosage , Lopinavir/administration & dosage , Male , Meropenem/administration & dosage , Middle Aged , Naproxen/administration & dosage , Oseltamivir/administration & dosage , Pneumonia, Viral/virology , Prednisolone/administration & dosage , Retrospective Studies , Ritonavir/administration & dosage , Treatment Outcome , Vancomycin/administration & dosage
17.
Int J Pharm ; 586: 119545, 2020 Aug 30.
Article in English | MEDLINE | ID: mdl-32553496

ABSTRACT

Amorphous solid dispersion (ASD) is a formulation strategy extensively used to enhance the bioavailability of poorly water soluble drugs. Despite this, they are limited by various factors such as limited drug loading, poor stability, drug-excipient miscibility and the choice of process platforms. In this work, we have developed a strategy for the manufacture of high drug loaded ASD (HDASD) using hot-melt extrusion (HME) based platform. Three drug-polymer combinations, indomethacin-Eudragit®E, naproxen-Eudragit®E and ibuprofen-Eudragit®E, were used as the model systems. The design spaces were predicted through Flory-Huggins based theory, and the selected HDASDs at pre-defined conditions were manufactured using HME and quench-cooled melt methods. These HDASD systems were also extensively characterised via small angle/wide angle x-ray scattering, differential scanning calorimetry, Infrared and Raman spectroscopy and atomic force microscopy. It was verified that HDASDs were successfully produced via HME platform at the pre-defined conditions, with maximum drug loadings of 0.65, 0.70 and 0.60 w/w for drug indomethacin, ibuprofen and naproxen respectively. Enhanced physical stability was further confirmed by high humidity (95%RH) storage stability studies. Through this work, we have demonstrated that by the implementation of predictive thermodynamic modelling, HDASD formulation design can be integrated into the HME process design to ensure the desired quality of the final dosage form.


Subject(s)
Ibuprofen/administration & dosage , Indomethacin/administration & dosage , Naproxen/administration & dosage , Polymethacrylic Acids/chemistry , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Drug Stability , Drug Storage , Excipients/chemistry , Humidity , Ibuprofen/chemistry , Indomethacin/chemistry , Naproxen/chemistry , Polymers/chemistry , Solubility , Thermodynamics
18.
Clin Orthop Surg ; 12(1): 86-93, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32117543

ABSTRACT

BACKGROUND: In drug therapy for patients with arthritis, a naproxen/esomeprazole combination drug may be a tolerable choice because it can minimize gastrointestinal and cardiovascular adverse effects. The aim of this study was to investigate the changes in quality of life (QOL), medication adherence, and satisfaction after switch from the existing drug to the combination drug. In addition, we analyzed the correlation between the above-mentioned variables and the stratified demographic and medical data of the patients. METHODS: A prospective, noninterventional, observational study was conducted in 30 hospitals between May 2014 and July 2016. In total, 2,308 patients with osteoarthritis, 99 patients with rheumatoid arthritis, and 76 patients with ankylosing spondylitis were enrolled. Demographic information (age, sex, body mass index [BMI], alcohol consumption, and smoking) and medical information (type of arthritis, duration of disease, and comorbidities) were collected via a self-administered questionnaire. Patients were observed for more than three months after switching to the combination drug. Data on the QOL (EuroQoL 5-Dimension questionnaire [EQ-5D questionnaire]), medication adherence (Morisky Medication Adherence Scale [MMAS]), and satisfaction were collected at the first and last visits. RESULTS: A total of 2,483 patients enrolled at 30 hospitals completed the questionnaire. After the switch to the combination drug, the mean EQ-5D score improved from 0.72 ± 0.17 to 0.79 ± 0.14 (p < 0.001), and significant improvement was associated with female sex (p = 0.016), shorter disease duration (p < 0.001), and absence of comorbidities (p < 0.001). The mean MMAS score was 6.38 ± 1.77, indicating medium adherence. Satisfaction was significantly higher in female patients (p < 0.001), in patients with a shorter disease duration (p < 0.001), osteoarthritis (p = 0.003), and no comorbidities (p < 0.001). Serious drug-related adverse effects did not occur. CONCLUSIONS: The overall QOL was improved with medium adherence after the switch to the combination drug. On the basis of the analysis of stratified data, sex, age, drinking, smoking, disease duration, comorbidities, and BMI might be associated with QOL, satisfaction, and adherence.


Subject(s)
Arthritis/drug therapy , Esomeprazole/administration & dosage , Naproxen/administration & dosage , Personal Satisfaction , Quality of Life , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Drug Combinations , Female , Humans , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires , Young Adult
19.
J Ocul Pharmacol Ther ; 36(6): 433-446, 2020.
Article in English | MEDLINE | ID: mdl-32023420

ABSTRACT

Purpose: The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide-co-glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium. Methods: NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 µm. Results: The drug loading efficiency of scaffolds was found to be higher than 84%, and about 90%-98% of NS was released at the end of 7 days with a fast drug release rate at the initial period of time and then in a slow and sustained manner. The corneal epithelial cells were isolated from New Zealand white rabbits. The obtained cells were seeded onto scaffolds and continued to increase during the time period of the study, indicating that the scaffolds might promote corneal epithelial cell proliferation without causing toxic effects for at least 10 days. Conclusions: The NS-loaded PLGA scaffolds exhibited a combination of controlled drug release and biomimetic properties that might be attractive for use in treatment of corneal damage both for controlled release and biomedical applications.


Subject(s)
Anti-Inflammatory Agents/pharmacokinetics , Corneal Injuries/drug therapy , Epithelium, Corneal/drug effects , Naproxen/pharmacokinetics , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Anti-Inflammatory Agents/administration & dosage , Biomimetics , Cell Proliferation/drug effects , Collagen/chemistry , Collagen/metabolism , Drug Compounding/methods , Drug Liberation , Epithelium, Corneal/pathology , Naproxen/administration & dosage , Polyethylene Glycols/chemistry , Polyethylene Glycols/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics , Polylysine/analogs & derivatives , Polylysine/chemistry , Polylysine/metabolism , Porosity/drug effects , Rabbits , Regeneration/drug effects , Regeneration/physiology
20.
Daru ; 28(1): 87-96, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31845157

ABSTRACT

BACKGROUND: Integrins are interesting targets in oncology. RGD sequence has high affinity for αVß3 integrin receptors. Diagnostic/therapeutic agents can be selectively delivered into cancer cells overexpressing αVß3 integrin by using RGD as a carrier. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown anticancer properties in in vitro and in vivo studies. The anti-cancer properties of NSAIDs occur though COX-2 inhibition. Regarding the anti-cancer properties of NSAIDs and overexpression of COX-2 enzyme in cancer cells, targeted delivery of NSAIDs into cancer cells to maximize their efficiency and minimize their side effects may gain increased clinical interest. OBJECTIVES: In this study, RGD was conjugated to ketoprofen/Naproxen to selectively transfer these non-selective COX inhibitors into cancer cells. METHODS: Keto/Nap-RGD-N4 peptides were synthesized based on solid phase fmoc peptide synthesis. Radiolabeling with [99mTc] via N4 (GGAG) ligand was done for biological evaluation. Affinity and specificity of Keto/Nap-RGD-N4 to integrin was determined using A2780, OVCAR-3, SKOV-3 and HT-1080 cell lines. Percentage of Intenalization was measured in A2780 cells. Biodistriburion was studied in normal and tumor model mice. RESULTS: Radiolabeled compounds showed high affinity to cells expressing αVß3 integrin in comparison to cells not expressing αVß3. The affinity to A2780 was significantly higher than OVCAR-3 cells. The %internalization into A2780 cells was quite low. Compounds showed more than 50% inhibition on A2780 and OVCAR-3 cells, less than 10% on MCF-7 and HT-1080 cells and no cytotoxicity on fibroblast cells after 48 h incubation. Although uptake of radiolabeled compounds in tumor was high at 1 h post-injection, the tumor/blood ratio was less than 1.5 which made SPECT imaging impossible. CONCLUSION: Provided that NSAID drugs are conjugated to RGD, there will be a selective delivery to target tissues as well as synergetic anti-tumor effects which reduce systemic doses and toxicity. Graphical abstract.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Antineoplastic Agents , Drug Delivery Systems , Integrin alphaVbeta3/metabolism , Ketoprofen , Naproxen , Oligopeptides , Radiopharmaceuticals , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Cell Line, Tumor , Female , Humans , Ketoprofen/administration & dosage , Ketoprofen/chemistry , Mice, Inbred BALB C , Mice, Nude , Naproxen/administration & dosage , Naproxen/chemistry , Neoplasms/metabolism , Oligopeptides/administration & dosage , Oligopeptides/chemistry , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/chemistry , Technetium , Tissue Distribution
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