- Regenerated cellulose capsules for controlled drug delivery: Part IV. In-vitro evaluation of novel self-pore forming regenerated cellulose capsules. [Journal Article]
- EJEur J Pharm Sci 2016 Dec 01
- In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC ca...
In the present work, the release mechanisms of active pharmaceutical ingredients (APIs) enclosed in self-pore forming regenerated cellulose (RC) two-piece hard shell capsules are described. The RC capsules were fabricated using a modified dip-coating approach, which yielded an assembled dosage form that was equivalent in size and shape to a conventional gelatin two-piece hard shell capsule. Drug release characteristics from RC capsules were evaluated using potassium chloride, diphenhydramine hydrochloride, tramadol hydrochloride, niacinamide, acetaminophen and ketoprofen as model APIs. The RC capsules act as a barrier coated reservoir device that releases the enclosed API at a zero order release rate. When comparing all the API's release behavior from RC capsules, a power-law relationship was observed between their zero-order release rates and their respective aqueous solubilities. Osmotic as well as diffusive mechanisms are involved in the release of the enclosed API. The osmotic mechanism's contribution to zero order release rate increases as the aqueous solubility of the tested APIs inside the capsule increases. The osmotic mediated flux and the apparent diffusivity of the APIs through the capsule wall is a competitive process and the osmotic mediated flux of the enclosed API begins to override its diffusivity through the capsule wall as the API solubility increases. This behavior is attributed to the wide range of pore sizes observed in RC membranes, from our prior analysis. The fluid permeability analysis shows that the RC capsules presented in this work may be better suited for osmotic drug delivery applications than conventional encapsulated systems described in the literature.
- Crystal structure and characterization of esterase Est25 mutants reveal improved enantioselectivity toward (S)-ketoprofen ethyl ester. [Journal Article]
- AMAppl Microbiol Biotechnol 2016 Dec 03
- Esterases comprise a group of enzymes that catalyze the cleavage and synthesis of ester bonds. They are important in biotechnological applications owing to their enantioselectivity, regioselectivity,...
Esterases comprise a group of enzymes that catalyze the cleavage and synthesis of ester bonds. They are important in biotechnological applications owing to their enantioselectivity, regioselectivity, broad substrate specificity, and the fact that they do not require cofactors. In a previous study, we isolated the esterase Est25 from a metagenomic library. Est25 showed catalytic activity toward the (R,S)-ketoprofen ethyl ester but had low enantioselectivity toward the (S)-ketoprofen ethyl ester. Because (S)-ketoprofen has stronger anti-inflammatory effects and fewer side effects than (R)-ketoprofen, enantioselectivity of this esterase is important. In this study, we generated Est25 mutants with improved enantioselectivity toward the (S)-ketoprofen ethyl ester; improved enantioselectivity of mutants was established by analysis of their crystal structures. The enantioselectivity of mutants was influenced by substitution of Phe72 and Leu255. Substituting these residues changed the size of the binding pocket and the entrance hole that leads to the active site. The enantioselectivity of Est25 (E = 1.1 ± 0.0) was improved in the mutants F72G (E = 1.9 ± 0.2), L255W (E = 16.1 ± 1.1), and F72G/L255W (E = 60.1 ± 0.5). Finally, characterization of Est25 mutants was performed by determining the optimum reaction conditions, thermostability, effect of additives, and substrate specificity after substituting Phe72 and Leu255.
- A review of the occurrence of pharmaceuticals and personal care products in Indian water bodies. [Review]
- EEEcotoxicol Environ Saf 2016 Dec 01; 137:113-120
- Little information exists on the occurrence and the ultimate fate of pharmaceuticals in the water bodies in India despite being one of the world leaders in pharmaceutical production and consumption. ...
Little information exists on the occurrence and the ultimate fate of pharmaceuticals in the water bodies in India despite being one of the world leaders in pharmaceutical production and consumption. This paper has reviewed 19 published reports of pharmaceutical occurrence in the aquatic environment in India [conventional activated sludge wastewater treatment plants (WTPs), hospital WTPs, rivers, and groundwater]. Carbamazepine (antipsychoactive), atenolol (antihypertensive), triclocarban and triclosan (antimicrobials), trimethoprim and sulfamethoxazole (antibacterials), ibuprofen and acetaminophen (analgesics), and caffeine (stimulant) are the most commonly detected at higher concentrations in Indian WTPs that treat predominantly the domestic sewage. The concentration of ciprofloxacin, sulfamethoxazole, amoxicillin, norfloxacin, and ofloxacin in Indian WTPs were up to 40 times higher than that in other countries in Europe, Australia, Asia, and North America. A very few studies in Indian rivers reported the presence of ciprofloxacin, enoxacin, ketoprofen, erythromycin, naproxen, ibuprofen, diclofenac and enrofloxacin. Similar compounds were reported in rivers in China, indicating a similar usage pattern in both of these developing countries. In a study reported from an open well in southern India, the groundwater showed the presence of cetirizine, ciprofloxacin, enoxacin, citalopram and terbinafine, which was close to a WTP receiving effluents from pharmaceutical production.
- Phytochemicals enhance antioxidant enzyme expression to protect against NSAID-induced oxidative damage of the gastrointestinal mucosa. [Review]
- MNMol Nutr Food Res 2016 Nov 24
- The gastrointestinal mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Non-steroidal anti-inflammatory drugs (NSAIDs), inc...
The gastrointestinal mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, indomethacin, and ketoprofen, are widely used in clinical medicine, but these drugs may cause oxidative stress, leading to gastrointestinal damage, such as ulcers. Lansoprazol, omeprazole, and other clinical drugs are widely used to treat duodenal and gastric ulcers and haven been shown to have multiple biological functions, such as antioxidant activity and the ability to upregulate antioxidant enzymes in vivo. Therefore, the reduction of oxidative stress may be an effective curative strategy for preventing and treating NSAID-induced ulcers of the gastrointestinal mucosa. Phytochemicals, such as dietary phenolic compounds, phenolic acids, flavan-3-ols, flavonols, flavonoids, gingerols, carotenes, and organosulfur, are common antioxidants in fruits, vegetables, and beverages. A large amount of evidence has demonstrated that natural phytochemicals possess bioactivity and potential health benefits, such as antioxidant, anti-inflammatory, and anti-bacterial benefits, and they can prevent digestive disease processes. In this review, we summarize the literature on phytochemicals with biological effects, such as angiogenic, anti-oxidant, anti-apoptotic, anti-inflammatory, and anti-ulceration effects, and their related mechanisms are also discussed. This article is protected by copyright. All rights reserved.
- Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach. [Journal Article]
- CSComput Struct Biotechnol J 2017; 15:1-7
- Alzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protec...
Alzheimer's disease (AD) represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive. In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database) simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin). Gene expression signatures were derived for disease from both blood (n = 344) and post-mortem brain (n = 690), and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level. These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness.
- Heart-cut achiral-chiral LC-LC method development using factorial design: application to the chiral separation of ketoprofen. [Journal Article]
- ABAnal Bioanal Chem 2016 Nov 19
- A two-dimensional achiral-chiral LC-LC method in heart-cut mode for ketoprofen and its enantiomeric fraction determination was proposed. A C8 column was used in the first dimension, and the chiral co...
A two-dimensional achiral-chiral LC-LC method in heart-cut mode for ketoprofen and its enantiomeric fraction determination was proposed. A C8 column was used in the first dimension, and the chiral column was an α1-acid glycoprotein. The mobile phase of the chiral system was optimized by a factorial design. The effect of temperature on retention and on enantiomeric resolution was studied. Particular attention was paid to mobile phase compatibility for the two columns and to transferring time, using ketoprofen standards. The R-(-) and S-(+)-ketoprofen retention times were 9 and 11 min, respectively; the resolution was higher than 1.1 and enantiomeric fraction close to 0.5. The method was applied to capsules and gels containing ketoprofen. Factorial design was also used to establish the best conditions for gel sample preparation. Recoveries were 84 and 105 % for capsules and gels, respectively. Graphical abstract Two-dimensional chromatogram for KPF and its enantiomers.
- Anaphylaxis after intravenous infusion of dexketoprofen trometamol. [Journal Article]
- TJTurk J Emerg Med 2016; 16(3):132-133
- Dexketoprofen trometamol (DT), a nonsteroidal anti-inflammatory drug, is a highly water-soluble salt and active enantiomer of rac-ketoprofen. Its parenteral form is commonly used for acute pain manag...
Dexketoprofen trometamol (DT), a nonsteroidal anti-inflammatory drug, is a highly water-soluble salt and active enantiomer of rac-ketoprofen. Its parenteral form is commonly used for acute pain management in emergency departments of our country. Side effects such as diarrhea, indigestion, nausea, stomach pain, and vomiting may be seen after the use of DT. Anaphylactic shock (AS) secondary to infusion of DT is very rare and, to our knowledge, it is the first case report describing this side effect. This case report was presented to emphasize that AS may be seen after the use of DT.
- Interactions of cephalexin with bovine serum albumin: displacement reaction and molecular docking. [Journal Article]
- BBioimpacts 2016; 6(3):125-133
- Introduction: The drug-plasma protein interaction is a fundamental issue in guessing and checking the serious drug side effects related with other drugs. The purpose of this research was to study the...
Introduction: The drug-plasma protein interaction is a fundamental issue in guessing and checking the serious drug side effects related with other drugs. The purpose of this research was to study the interaction of cephalexin with bovine serum albumin (BSA) and displacement reaction using site probes. Methods: The interaction mechanism concerning cephalexin (CPL) with BSA was investigated using various spectroscopic methods and molecular modeling method. The binding sites number, n, apparent binding constant, K, and thermodynamic parameters, ΔG(0), ΔH(0), and ΔS(0) were considered at different temperatures. To evaluate the experimental results, molecular docking modeling was calculated. Results: The distance, r=1.156 nm between BSA and CPL were found in accordance with the Forster theory of non-radiation energy transfer (FRET) indicating energy transfer occurs between BSA and CPL. According to the binding parameters and ΔG(0)= negative values and ΔS(0)= 28.275 j mol(-1)K(-1), a static quenching process is effective in the CPL-BSA interaction spontaneously. ΔG(0) for the CPL-BSA complex obtained from the docking simulation is -28.99 kj mol(-1), which is close to experimental ΔG of binding, -21.349 kj mol(-1) that indicates a good agreement between the results of docking methods and experimental data. Conclusion: The outcomes of spectroscopic methods revealed that the conformation of BSA changed during drug-BSA interaction. The results of FRET propose that CPL quenches the fluorescence of BSA by static quenching and FRET. The displacement study showed that phenylbutazon and ketoprofen displaced CPL, indicating that its binding site on albumin is site I and Gentamicin cannot be displaced from the binding site of CPL. All results of molecular docking method agreed with the results of experimental data.
- Photocages for protection and controlled release of bioactive compounds. [Journal Article]
- CCChem Commun (Camb) 2016 Dec 06; 52(99):14215-14218
- Using a sunscreen-based photocage, we have demonstrated that it is possible to prevent photodegradation of a bioactive compound and to achieve its controlled photorelease. The concept has been proven...
Using a sunscreen-based photocage, we have demonstrated that it is possible to prevent photodegradation of a bioactive compound and to achieve its controlled photorelease. The concept has been proven linking avobenzone, one of the most important UVA blockers, to ketoprofen, which is a representative example of a photosensitive drug.
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- Systematically Optimized Ketoprofen-Loaded Novel Proniosomal Formulation for Periodontitis: In Vitro Characterization and In Vivo Pharmacodynamic Evaluation. [Journal Article]
- APAAPS PharmSciTech 2016 Nov 14
- Various preclinical/clinical studies support the effectiveness of ketoprofen in periodontitis; however, the literature reveals that novel delivery systems have been less explored for the drug in peri...
Various preclinical/clinical studies support the effectiveness of ketoprofen in periodontitis; however, the literature reveals that novel delivery systems have been less explored for the drug in periodontitis. The current investigation aims to explore the potential of a pro-vesicular approach-based proniosomal drug delivery of ketoprofen for its effectiveness and validation in experimental periodontal disease (EPD). Formulations were developed using I-optimal mixture design. Developed formulations were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Selected proniosomal gels were evaluated for mucoadhesiveness, ex vivo drug permeation, and retention studies. Optimized proniosomal gel was evaluated for surface morphology, rheological behavior, texture studies, and pharmacodynamic activity in EPD. The results showed that ketoprofen-loaded proniosomal formulations formed a mucoadhesive hydrogel comprising spherical and flexible vesicles. Viscosity and texture studies showed good adhesion and smoothness, which are desired for enhanced permeation. The disease condition was improved with preserved bone resorption process, that too with intact cementum vis-à-vis marketed gel formulation, when evaluated in the EPD model. The results lead to the conclusion that proniosomes can act as a promising carrier and can be effectively used for improved ketoprofen delivery in periodontal pockets.