Search results for: low solubility drugs

Authors: Ponchang Apollos Wuyep, Alice Njolke Mafe, Longchi Satkat Zacheaus, Dogun Ojochogu, Dabot Ayuba Yakubu

Abstract:

Fungi causes huge losses when infections occur both in plants and animals. Synthetic Antifungal drugs are mostly very expensive and highly cytotoxic when taken. This study was aimed at determining the in vitro and in vivo antifungal activities of the leaves and stem extracts of Terminalia mantaly (Umbrella tree)H. Perrier on Aspergillus species in a bid to identify potential sources of cheap starting materials for the synthesis of new drugs to address the growing antimicrobial resistance. T. mantaly leave and stem powdered plant was extracted by fractionation using the method of solvent partition co-efficient in their graded form in the order n-hexane, Ethyl acetate, methanol and distilled water and phytochemical screening of each fraction revealed the presence of alkaloids, saponins, Tannins, flavonoids, carbohydrates, steroids, anthraquinones, cardiac glycosides and terpenoids in varying degrees. The Agar well diffusion technique was used to screen for antifungal activity of the fractions on clinical isolates of Aspergillus species (Aspergillus flavus and Aspergillus fumigatus). Minimum inhibitory concentration (MIC50) of the most active extracts was determined by the broth dilution method. The fractions test indicated a high antifungal activity with zones of inhibition ranging from 6 to 26 mm and 8 to 30mm (leave fractions) and 10mm to 34mm and 14mm to36mm (stem fractions) on A. flavus and A. fumigatus respectively. All the fractions indicated antifungal activity in a dose response relationship at concentrations of 62.5mg/ml, 125mg/ml, 250mg/ml and 500mg/ml. Better antifungal efficacy was shown by the Ethyl acetate, Hexane and Methanol fractions in the in vitro as the most potent fraction with MIC ranging from 62.5 to 125mg/ml. There was no statistically significant difference (P>0.05) in the potency of the Eight fractions from leave and stem (Hexane, Ethyl acetate, methanol and distilled water, antifungal (fluconazole), which served as positive control and 10% DMSO(Dimethyl Sulfoxide)which served as negative control. In the in vivo investigations, the ingestion technique was used for the infectious studies Female Drosophilla melanogaster(UAS-Diptericin)normal flies(positive control),infected and not treated flies (negative control) and infected flies with A. fumigatus and placed on normal diet, diet containing fractions(MSM and HSM each at concentrations of 10mg/ml 20mg/ml, 30mg/ml, 40mg/ml, 50mg/ml, 60mg/ml, 70mg/ml, 80mg/ml, 90mg/ml and 100mg/ml), diet containing control drugs(fluconazole as positive control)and infected flies on normal diet(negative control), the flies were observed for fifteen(15) days. Then the total mortality of flies was recorded each day. The results of the study reveals that the flies were susceptible to infection with A. fumigatus and responded to treatment with more effectiveness at 50mg/ml, 60mg/ml and 70mg/ml for both the Methanol and Hexane stem fractions. Therefore, the Methanol and Hexane stem fractions of T. mantaly contain therapeutically useful compounds, justifying the traditional use of this plant for the treatment of fungal infections.

Keywords: Terminalia mantaly, Aspergillus fumigatus, cytotoxic, Drosophila melanogaster, antifungal

Procedia PDF Downloads 59

Authors: Adil Mustafa, Ahmet Erten, Alper Kiraz, Melikhan Tanyeri

Abstract:

Work presented here is based on a novel experimental technique used to hydrodynamically trap oil microdroplets inside a microfluidic chip at the junction of microchannels known as stagnation point. Hydrodynamic trapping has been recently used to trap and manipulate a number of particles starting from microbeads to DNA and single cells. Benzyl Benzoate (BB) is used as droplet material. The microdroplets are trapped individually at stagnation point and their dissolution was observed. Experiments are performed for two concentrations (10mM or 10µM) of AOT surfactant (Docusate Sodium Salt) and two flow rates for each case. Moreover, experimental data is compared with Zhang-Yang-Mao (ZYM) model which studies dissolution of liquid microdroplets in the presence of a host fluid experiencing extensional creeping flow. Industrial processes like polymer blending systems in which heat or mass transport occurs experience extensional flow and an insight into these phenomena is of significant importance to many industrial processes. The experimental technique exploited here gives an insight into the dissolution of liquid microdroplets under extensional flow regime. The comparison of our experimental results with ZYM model reveals that dissolution of microdroplets at lower surfactant concentration (10µM) fits the ZYM model at saturation concentration (Cs) value reported in literature (Cs = 15×10⁻³Kg\m³) while for higher surfactant concentration (10mM) which is also above the critical micelle concentration (CMC) of surfactant (5mM) the data fits ZYM model at (Cs = 45×10⁻³Kg\m³) which is 3X times the value reported in literature. The difference in Cs value from the literature shows enhancement in dissolution rate of sparingly soluble BB microdroplets at surfactant concentrations higher than CMC. Enhancement in the dissolution of sparingly soluble materials is of great importance in pharmaceutical industry. Enhancement in the dissolution of sparingly soluble drugs is a key research area for drug design industry. The experimental method is also advantageous because it is robust and has no mechanical contact with droplets under study are freely suspended in the fluid as compared existing methods used for testing dissolution of drugs. The experiments also give an insight into CMC measurement for surfactants.

Keywords: extensional flow, hydrodynamic trapping, Zhang-Yang-Mao, CMC

Procedia PDF Downloads 326

Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

Abstract:

Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

Procedia PDF Downloads 234

Authors: Ikram Kamal, Mohamed Blaghen

Abstract:

Pollution caused by petroleum hydrocarbons in terrestrial and aquatic environment is a common phenomenon that causes significant ecological and social problems. Biosurfactant applications in the environmental industries are promising due to their biodegradability, low toxicity and effectiveness in enhancing biodegradation and solubilization of low solubility compounds. Currently, the main application is for enhancement of oil recovery and hydrocarbon bioremediation due to their biodegradability and low critical micelle concentration (CMC). In this study we have investigated the potential of bacterial strains collected aseptically from the lagoon Marchika (water and soil) in Nador, Morocco; for the production of biosurfactants. This study also aimed to optimize the biosurfactant production process by changing the variables that influence the type and amount of biosurfactant produced by these microorganisms such as: carbon sources and also other physical and chemical parameters such as temperature and pH. Emulsification index, methylene blue test and thin layer chromatography (TLC) revealed the ability of strains used in this study to produce compounds that could emulsify gasoline. In addition a GC/MS was used to separate and identify different biosurfactants purified.

Keywords: petroleum hydrocarbons, biosurfactant, biodegradability, critical micelle concentration, lagoon Marchika

Procedia PDF Downloads 335

Authors: Siddharth Vishwakarma, Danie Shajie A., Mishra H. N.

Abstract:

Milk powder becomes very useful in the low milk supply area but the exact amount to add for one glass of milk and the handling is difficult. So, the idea of instant soluble milk tablet comes into existence for its high solubility and easy handling. The moisture content of milk tablets is increased by the direct addition of water with no additives for binding. The variation of the tensile strength of instant soluble milk tablets and the flowability of milk powder with the moisture content is analyzed and optimized for the highest tensile strength of instant soluble milk tablets and flowability, above a particular value of milk powder using response surface methodology. The flowability value is necessary for ease in quantifying the milk powder, as a feed, in the designed tablet making machine. The instant soluble nature of milk tablets purely depends upon the disintegration characteristic of tablets in water whose study is under progress. Conclusions: The optimization results are very useful in the commercialization of milk tablets.

Keywords: flowability, milk powder, response surface methodology, tablet making machine, tensile strength

Procedia PDF Downloads 159

Authors: Yuliani Aisyah, Sri Haryani, Novi Safriani

Abstract:

Nutmeg oil is one of the essential oils that have the ability as an antibacterial so it potentially uses to inhibit the growth of undesirable microbes in food. However, the essential oil that has low solubility in water, high volatile content, and strong aroma properties is difficult to apply in to foodstuffs. Therefore, the oil-in-water nanoemulsion system was used in this research. Gelatin, lecithin and tween 80 with 10%, 20%, 30% concentrations have been examined for the preparation of nutmeg oil nanoemulsions. The physicochemical properties and stability of nutmeg oil nanoemulsion were analyzed on viscosity, creaming index, emulsifying activity, droplet size, and polydispersity index. The results showed that the type and concentration stabilizer had a significant effect on viscosity, creaming index, droplet size and polydispersity index (P ≤ 0,01). The nanoemulsions stabilized with tween 80 had the best stability because the creaming index value was 0%, the emulsifying activity value was 100%, the droplet size was small (79 nm) and the polydispersity index was low (0.10) compared to the nanoemulsions stabilized with gelatin and lecithin. In brief, Tween 80 is strongly recommended to be used for stabilizing nutmeg oil nanoemulsions.

Keywords: nanoemulsion, nutmeg oil, stabilizer, stability

Procedia PDF Downloads 138

Authors: Bilal Ahmad Ashwar, Asima Shah, S. A. Rather, Asir Gani, S.M. Wani, I.D. Wani, F. A. Masoodi, Adil Gani

Abstract:

Starches isolated from two newly released rice varieties (K-322 & K-448) were subject to irradiation at 0, 5, 10, and 20 kGy doses. Comparative study between native (not irradiated) and irradiated starch samples was carried out to evaluate the changes in physicochemical, morphological and pasting properties due to gamma irradiation. Significant decrease was found in apparent amylose content, pH, swelling power, syneresis, and pasting properties, whereas carboxyl content, water absorption capacity, transmittance and solubility were found to increase with the increase in irradiation dose. Granule morphology of native and irradiated starches under scanning electron microscope revealed that granules were polygonal or irregular in shape. The starch granules were somewhat deformed by gamma irradiation. X-ray diffraction pattern showed A type of pattern in native as well as irradiated starches.

Keywords: rice starch, gamma irradiation, morphological properties, pasting properties, physicochemical properties.

Procedia PDF Downloads 451

Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

Abstract:

Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

Procedia PDF Downloads 648

Authors: Mazaher Yarmohamadi-Vasel, Ali Reza Modarresi-Alama, Sahar Shabzendedara

Abstract:

Purpose/Objectives: The first purpose was synthesize Poly(N-(sulfophenyl)aniline) nanoflowers (PSANFLs) and Poly(N-(sulfophenyl)aniline) nanofibers/titanium dioxide nanoparticles ((PSANFs/TiO2NPs) by a solid-state mechano-chemical reaction and template-free method and use them in hybrid solar cell. Also, our second aim was to increase the solubility and the processability of conjugated nanomaterials in water through polar functionalized materials. poly[N-(4-sulfophenyl)aniline] is easily soluble in water because of the presence of polar groups of sulfonic acid in the polymer chain. Materials/Methods: Iron (III) chloride hexahydrate (FeCl3∙6H2O) were bought from Merck Millipore Company. Titanium oxide nanoparticles (TiO2, <20 nm, anatase) and Sodium diphenylamine-4-sulfonate (99%) were bought from Sigma-Aldrich Company. Titanium dioxide nanoparticles paste (PST-20T) was prepared from Sharifsolar Co. Conductive glasses coated with indium tin oxide (ITO) were bought from Xinyan Technology Co (China). For the first time we used the solid-state mechano-chemical reaction and template-free method to synthesize Poly(N-(sulfophenyl)aniline) nanoflowers. Moreover, for the first time we used the same technique to synthesize nanocomposite of Poly(N-(sulfophenyl)aniline) nanofibers and titanium dioxide nanoparticles (PSANFs/TiO2NPs) also for the first time this nanocomposite was synthesized. Examining the results of electrochemical calculations energy gap obtained by CV curves and UV–vis spectra demonstrate that PSANFs/TiO2NPs nanocomposite is a p-n type material that can be used in photovoltaic cells. Doctor blade method was used to creat films for three kinds of hybrid solar cells in terms of different patterns like ITO│TiO2NPs│Semiconductor sample│Al. In the following, hybrid photovoltaic cells in bilayer and bulk heterojunction structures were fabricated as ITO│TiO2NPs│PSANFLs│Al and ITO│TiO2NPs│PSANFs /TiO2NPs│Al, respectively. Fourier-transform infrared spectra, field emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectra, cyclic voltammetry (CV) and electrical conductivity were the analysis that used to characterize the synthesized samples. Results and Conclusions: FE-SEM images clearly demonstrate that the morphology of the synthesized samples are nanostructured (nanoflowers and nanofibers). Electrochemical calculations of band gap from CV curves demonstrated that the forbidden band gap of the PSANFLs and PSANFs/TiO2NPs nanocomposite are 2.95 and 2.23 eV, respectively. I–V characteristics of hybrid solar cells and their power conversion efficiency (PCE) under 100 mWcm−2 irradiation (AM 1.5 global conditions) were measured that The PCE of the samples were 0.30 and 0.62%, respectively. At the end, all the results of solar cell analysis were discussed. To sum up, PSANFLs and PSANFLs/TiO2NPs were successfully synthesized by an affordable and straightforward mechanochemical reaction in solid-state under the green condition. The solubility and processability of the synthesized compounds have been improved compared to the previous work. We successfully fabricated hybrid photovoltaic cells of synthesized semiconductor nanostructured polymers and TiO2NPs as different architectures. We believe that the synthesized compounds can open inventive pathways for the development of other Poly(N-(sulfophenyl)aniline based hybrid materials (nanocomposites) proper for preparing new generation solar cells.

Keywords: mechanochemical synthesis, PSANFLs, PSANFs/TiO2NPs, solar cell

Procedia PDF Downloads 47

Authors: S. Benessam, T. H. Debieche, S. Amiour, A. Chine, S. Khelili

Abstract:

The metallic trace elements (MTE) are present in water and sediments of the rivers with weak concentrations. Several physicochemical parameters (Eh, pH and oxygen dissolved) and chemical processes (adsorption, absorption, complexation and precipitation) as well as nature of the sediments control their mobility. In order to determine the effect of these factors on the mobility of some MTE (Cd, Cr, Cu, Fe, Pb and Zn) in water of the rivers, a two-monthly monitoring of the physicochemical parameters and chemistry of water and sediments of the Nil wadi (Algeria) was carried out during the period from November 2013 to January 2015. The results show that each MTE has its own conditions of mobility and generally are very influence by the variations of the pH and Eh. Under the natural conditions, neutral pH with basic and medium oxidizing, only the lead presented in water with raised values, indicating its solubility in water and its salting out of the sediments. The other MTE present raised concentrations in the sediments, indicating their trapping by adsorption and/or chemical precipitation. The chemical form of each ETM was given by Eh-pH diagrams. The spatio-temporal monitoring of these ETM shows the effect of the rains, the dry periods and the rejects in the variation of their concentrations.

Keywords: chemistry, metallic trace elements, sediment, water

Procedia PDF Downloads 266

Authors: Deokyeong Choe, Sung Hun Youn, Younggon Kim, Chul Soo Shin

Abstract:

L-Cysteine, a sulfur-containing amino acid, has been often used in the pharmaceutical, cosmetic, food, and feed additive industries. This amino acid has been usually produced by acid-hydrolysis of human hair and poultry feathers. There are many problems, such as avoidance for use of animal hair, low yields, and formation of harmful waste material. As an alternative, the enzymatic conversion of D, L-2-amino-Δ2-thiazoline-4-carboxylic acid (ATC) to L-cysteine has been developed as an environmental-friendly method. However, the substrate solubility was too low to be used in industry. In this study, high concentrations of eutectic substrate solutions were prepared to solve the problem. Eutectic melting occurred at 39°C after mixing ATC and malonic acid at a molar ratio of 1:1. The characteristics of eutectic mixtures were analyzed by FE-SEM, EDS mapping, and XPS. However, since sorbitol, MnSO4, and NaOH should be added as supplements to the substrate mixture for the activation and stabilization of the enzyme, strategies for sequential addition of total five compounds, ATC, malonic acid, sorbitol, MnSO4, and NaOH were established. As a result, eutectic substrate mixtures of 670 mM ATC were successfully formulated. After 6 h of enzymatic reaction, 550 mM L-cysteine was made.

Keywords: D, L-2-amino-Δ2-thiazoline-4-carboxylicacid, enzymatic conversion, eutectic solution, l-cysteine

Procedia PDF Downloads 412

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder, to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 63

Authors: Samiul Islam Hazarika, Domngam Boje, Ananta Kumar Atta

Abstract:

It is well familiar that solvents play a significant role in modern chemistry. Solvents can change the reactivity and physicochemical properties of molecules in a solution. Keeping this in mind, we have designed and synthesized a mono-triazolyl-linked pyrenyl-appended xylofuranose derivative for the detection of metal ions with changing solvent systems. The incorporation of a sugar backbone in the sensor increases the water solubility and biocompatibility. The experimental study revealed that the xylofuranose-based fluorescence probe did not exhibit any specific selectivity towards metal ions in acetonitrile (CH₃CN) solvent. Whereas, we revealed that triazole-linked pyrenyl-appended xylofuranose-based fluorescent sensor would exhibit high selectivity and sensitivity towards Au³⁺ ions in CH₃CN-H₂O (1/1, v/v) system. This observation might be explained by the viscosity and polarity differences of CH₃CN and CH₃CN-H₂O solvent systems. The formation of the sensor-Au³⁺ complex was also established by high-resolution mass spectrometry (HRMS) data of the complex.

Keywords: triazole, furanose, fluorometric, solvent dependent

Procedia PDF Downloads 103

Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

Abstract:

Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

Procedia PDF Downloads 291

Authors: Fatmawati Adam, Saidatul Syaima Mat Tari, Saiful Nizam Tajuddin, Nurul Salwa Azliyana Hamzah

Abstract:

Essential oil of agarwood or known as Gaharu in Malay is highly prized for its value as luxury fragrances and incense. However, the complexities of the chemical composition of agarwood itself is the main challenge for establishment of an effective recovery method, which is able to ensure uniform qualities and standard for each batch of essential oil production. Agarwood markers are actually a blend of volatile and non-volatile compounds. While volatile molecules could be easily retrieved by the present distillation technique, the high solubility properties are the limiting factor for the latter. With regard to this, an elementary chemistry resolution study had been performed on commercial agarwood essential oil-water mixture, by the application of preparative HPLC and FTIR. Interpretation of the results leads to the theoretical postulation that, agarwood water mixture comprise of agarospirol, jinkohol, jinkoh eremol and khusenol. This study provides a pinpoint on the chemical characteristics of water soluble (non-volatile) agarwood compounds, therefore, will be an insight for researchers to develop a more strategic technique for their extraction. Thereafter the optimum quality of this essential oil could be controlled in a more improved way.

Keywords: Agarwood, Aquillaria Malaccensis, agarospirol, jinkohol, jinkoh eremol, khusenol

Procedia PDF Downloads 533

Authors: Adeline Meriaux, Claire Gaiani, Jennifer Burgain, Frantz Fournier, Lionel Muniglia, Jérémy Petit

Abstract:

Spray-drying process is widely used for the production of dairy powders for food and pharmaceuticals industries. It involves the atomization of a liquid feed into fine droplets, which are subsequently dried through contact with a hot air flow. The resulting powders permit transportation cost reduction and shelf life increase but can also exhibit various interesting functionalities (flowability, solubility, protein modification or acid gelation), depending on operating conditions and milk composition. Indeed, particles porosity, surface composition, lactose crystallization, protein denaturation, protein association or crust formation may change. Links between spray-drying conditions and physicochemical and functional properties of powders were investigated by a design of experiment methodology and analyzed by principal component analysis. Quadratic models were developed, and multicriteria optimization was carried out by the use of genetic algorithm. At the time of abstract submission, verification spray-drying trials are ongoing. To perform experiments, milk from dairy farm was collected, skimmed, froze and spray-dried at different air pressure (between 1 and 3 bars) and outlet temperature (between 75 and 95 °C). Dry matter, minerals content and proteins content were determined by standard method. Solubility index, absorption index and hygroscopicity were determined by method found in literature. Particle size distribution were obtained by laser diffraction granulometry. Location of the powder color in the Cielab color space and water activity were characterized by a colorimeter and an aw-value meter, respectively. Flow properties were characterized with FT4 powder rheometer; in particular, compressibility and shearing test were performed. Air pressure and outlet temperature are key factors that directly impact the drying kinetics and powder characteristics during spray-drying process. It was shown that the air pressure affects the particle size distribution by impacting the size of droplet exiting the nozzle. Moreover, small particles lead to more cohesive powder and less saturated color of powders. Higher outlet temperature results in lower moisture level particles which are less sticky and can explain a spray-drying yield increase and the higher cohesiveness; it also leads to particle with low water activity because of the intense evaporation rate. However, it induces a high hygroscopicity, thus, powders tend to get wet rapidly if they are not well stored. On the other hand, high temperature provokes a decrease of native serum proteins, which is positively correlated to gelation properties (gel point and firmness). Partial denaturation of serum proteins can improve functional properties of powder. The control of air pressure and outlet temperature during the spray-drying process significantly affects the physicochemical and functional properties of powder. This study permitted to better understand the links between physicochemical and functional properties of powder to identify correlations between air pressure and outlet temperature. Therefore, mathematical models have been developed, and the use of genetic algorithm will allow the optimization of powder functionalities.

Keywords: dairy powders, spray-drying, powders functionalities, design of experiment

Procedia PDF Downloads 49

Authors: Hamidreza Sharifan, Audra Morse

Abstract:

Accurate assessments of contaminant concentrations based on traditional grab sampling methods are not always possible. Passive samplers offer an attractive alternative to traditional sampling methods that overcomes these limitations. The POCIS approach has been used as a screening tool for determining the presence/absence, possible sources and relative amounts of organic compounds at field sites. The objective for the present research is on mass transfer of five water contaminants (atrazine, caffeine, bentazon, ibuprofen, atenolol) through the Water Boundary Layer (WBL) and membrane. More specific objectives followed by establishing a relationship between the sampling rate and water solubility of the compounds, as well as comparing the molecular weight of the compounds and concentration of the compounds at the time of equilibrium. To determine whether water boundary layer effects transport rate through the membrane is another main objective in this paper. After GC mass analysis of compounds, regarding the WBL effect in this experiment, Sherwood number for the experimental tank developed. A close relationship between feed concentration of compound and sampling rate has been observed.

Keywords: passive sampler, water contaminants, PES-transfer rate, contaminant concentrations

Procedia PDF Downloads 439

Authors: D. Baranova, E. Neborak

Abstract:

Polyphenols, particularly flavonoids like quercetin, fisetin, and kaempferol, have gained significant attention in nutrition due to their antioxidant, senolytic, and anti-inflammatory properties. These compounds are commonly found in various plant-based foods and are represented by diverse subclasses, each with unique health benefits. Understanding their absorption, metabolism, and bioactivity within the human body is crucial for unlocking their full potential. Quercetin, for instance, exists in multiple forms, impacting its solubility and absorption in the intestine. Its intake, often derived from sources like apples, is affected by cooking methods, with medium heat retaining its potency. Fisetin, also present in fruits and vegetables, demonstrates neuroprotective qualities and stability under varied conditions compared to quercetin. Similarly, kaempferol, found in fruits and vegetables, displays antioxidative effects but is influenced by cooking techniques, with specific methods preserving its polyphenolic content better. Overall, these polyphenols offer promising health benefits, yet their optimal dosage and specific dietary recommendations warrant further research to harness their full nutritional potential.

Keywords: polyphenols, flavonoids, absorption, quercetin, kaempferol, fisetin, senolytics, absorption, cooking method

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Sokratis Koskinakis, Georgia Frakolaki, Magdalini Krokida

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Regular consumption of omega-3 fatty acid-rich lipids is said to provide a wide range of health benefits, including prevention of inflammation, cardiovascular disease, diabetes, arthritis, and ulcerative colitis. Because of their potential nutritional and health benefits, the omega-3 PUFAs are increasingly being supplemented in functional food products meant to improve human health and wellbeing. However, dietary fortification with PUFAs is difficult due to their low water solubility, tendency to oxidize quickly, and inconsistent bioavailability. These issues can be solved through application of modern encapsulation technologies, which typically entail integrating omega-3 oils into well-designed matrices made from food-grade components. Electrospinning, for example, is an effective encapsulation method for producing sub-micron or nano-scale polymer fibers. For this purpose, various combinations of hydroxypropyl-β-cyclodextrin and cellulose nanocrystals/ nanofibers were assessed for the encapsulation of omega-3 fatty acids through the innovative technology of electrospinning. The encapsulation yield was evaluated through GC-analysis, and the morphology of the final products was assessed through SEM analysis.

Keywords: electrospinning, encapsulation, omega-3 fatty acids, cellulose nanocrystals / nanofibers

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Authors: Thippharat Wongsilarat, Parichat tuntilanon, Chonlakan Prataksitorn

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Recurrent adverse drug reactions are harmful to patients with mild to fatal illnesses, and affect not only patients but also their relatives, and organizations. To compare safe use of medicine among patients before and after using the recurrent adverse drug reaction prevention program . Quasi-experimental research with the target population of 598 patients with drug allergy history. Data were collected through an observation form tested for its validity by three experts (IOC = 0.87), and analyzed with a descriptive statistic (percentage). The research was conducted jointly with a multidisciplinary team to analyze and determine the weak points and strong points in the recurrent adverse drug reaction prevention system during the past three years, and 546, 329, and 498 incidences, respectively, were found. Of these, 379, 279, and 302 incidences, or 69.4; 84.80; and 60.64 percent of the patients with drug allergy history, respectively, were found to have caused by incomplete warning system. In addition, differences in practice in caring for patients with drug allergy history were found that did not cover all the steps of the patient care process, especially a lack of repeated checking, and a lack of communication between the multidisciplinary team members. Therefore, the recurrent adverse drug reaction prevention program was developed with complete warning points in the information technology system, the repeated checking step, and communication among related multidisciplinary team members starting from the hospital identity card room, patient history recording officers, nurses, physicians who prescribe the drugs, and pharmacists. Including in the system were surveillance, nursing, recording, and linking the data to referring units. There were also training concerning adverse drug reactions by pharmacists, monthly meetings to explain the process to practice personnel, creating safety culture, random checking of practice, motivational encouragement, supervising, controlling, following up, and evaluating the practice. The rate of prescribing drugs to which patients were allergic per 1,000 prescriptions was 0.08, and the incidence rate of recurrent drug reaction per 1,000 prescriptions was 0. Surveillance of recurrent adverse drug reactions covering all service providing points can ensure safe use of medicine for patients.

Keywords: recurrent drug, adverse reaction, safety, use of medicine

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Authors: Yohannes Kelifa, Gomathi Periasamy, Aman Karim

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Introduction: Diabetes mellitus has become a major public health and economical problem across the globe. Modern antidiabetic drugs have a number of limitations, and scientific investigation of traditional herbal remedies used for diabetes may provide novel leads for the development of new antidiabetic drugs that can be used as alternative or complementary to available antidiabetic allopathic medications. Though Myrica salicifolia Hochst. ex A. Rich. is used for the management of diabetes in Ethiopian traditional medicine, there was no previous scientific evidence about its antidiabetic effect to the authors’ knowledge. This study was undertaken to evaluate the antidiabetic activity the root extracts of Myrica salicifolia in streptozotocin (STZ)-induced diabetic mice. Methods: Experimental diabetes was induced by intraperitoneal administration of STZ (150 mg/kg) in male mice. Diabetic mice were treated with oral doses of M. salicifolia root extracts at 200, 400 and 600 mg/kg, and its fractions (chloroform, ethyl acetate, n-butanol and aqueous) at a dose of 400 mg/kg daily for 15 days. Fasting blood glucose level (BGL) was measured at 0, 5th,10th, and 15th day. The free radical scavenging activity of the crude extract was determined using in vitro by DPPH assay. The statistical significance was assessed by one-way ANOVA, followed by Tukey’s multiple comparison tests. Results were considered significant when p < 0.05. Results: Daily administration of the M. salicifolia 80% methanol root extracts (at three different doses (200, 400 and 600 mg/kg) significantly (p < 0.05, p < 0.01 and p < 0.001) reduced fasting BGL compared with diabetic control. The aqueous and butanol fractions at a dose of 400 mg/kg resulted in maximum reduction of fasting BGL by 42.39%, and 52.13%, respectively at the 15th day in STZ-induced diabetic mice. Free radical scavenging activity of the 80% methanol extract of M. salicifolia was comparable to ascorbic acid. The IC50 values of the crude extract and ascorbic acid (a reference compound) were found to be 4.54 μg/ml and 4.39 μg/ml, respectively. Conclusion: These findings demonstrated that the methanolic extracts of M. salicifolia root and its fractions (n-butanol and aqueous) exhibit a significant antihyperglycemic activity in STZ-induced diabetic mice. Furthermore, the result of the present study indicates that M. salicifolia root extract is a potential source of natural antioxidants.

Keywords: antidiabetic, diabetes mellitus, DPPH, mice, Myrica salicifolia, streptozotocin

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Authors: Kalakotla Shanker, G. Krishna Mohan

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Nowadays, nanoparticles are being used in pharmacological studies for their exclusive properties such as small size, more surface area, biocompatibility and enhanced solubility. In view of this, the present study aimed to evaluate the antihyperglycemic potential of biologically synthesized silver nanoparticles (BSSNPs) and Gymnema sylvestre (GS) extract. The SEM and SEM analysis divulges that the BSSNPs were spherical in shape. EDAX spectrum exhibits peaks for the presence of silver, carbon, and oxygen atoms in the range of 1.0-3.1 keV. FT-IR reveals the binding properties of active bio-constituents responsible for capping and stabilizing BSSNPs. The results showed increased blood glucose, huge loss in body weight and downturn in plasma insulin. The GS extract (200 mg/kg, 400 mg/kg), BSSNPs (100 mg/kg, 200 mg/kg) and metformin 50 mg/kg were administered to the diabetic rats. BSSNPs at a dose level of 200 mg/kg (b.wt.p.o.) showed significant inhibition of (p<0.001) blood glucose levels as compared with GS extract treated group. The results obtained from study indicate that the BSSNP shows potent anti-diabetic activity.

Keywords: biological silver nanoparticles, G. sylvetre, gymnemic acid, streptozotocin, Wistar rats, antihyperglycemic activity, anti-hyperlipidemic activity

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Authors: Nisrine Benzbiria, Abderrahmane Thoume, Mustapha Zertoubi

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The goal of this research is to investigate the corrosion inhibition potential of functionalized graphene oxide (GO) with oxime derivative on AA2024-T3 surface in synthetic seawater. The utilization of functionalized graphene oxide is creating a category of corrosion inhibitors known as organically modified nanomaterials. In our work, the functionalization of GO by chalcone oxime enables graphene oxide to have enhanced water solubility and a good corrosion mitigation capacity. Fourier-transform infrared (FT-IR) spectroscopy was utilized to evaluate the main functional groups of the inhibitor. Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization curves (PDP) showed that the inhibitor acts as a mixed-type inhibitor. The inhibitory efficiency (IE) improved as the concentration increased to a value of 96% after one hour of exposure to a medium containing 60 mg/L ppm of the inhibitor. According to thermodynamic calculations, the adsorption of the inhibitor on the AA2024-T3 surface in 3% NaCl followed the Langmuir isotherm. The formation of a barrier layer was further confirmed by surface analysis. The protective film prevented the alloy dissolution and limited the accessibility of attacking ions, as evinced by solution analysis techniques.

Keywords: AA2024-T3, NaCl, electrochemical methods, FT-IR, SEM/AFM, DFT, MC simulation

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Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 70

Authors: Ana M. Prieto del Pino

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As is well known, UN Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (1988) was a landmark regarding the seizure of proceeds of crime. Depriving criminals of the profits from their activity became a priority at an international level in the fight against organised crime. Enabling confiscation of proceeds of illicit traffic in narcotic drugs and psychotropic substances, criminalising money laundering and confiscating the proceeds thereof are the three measures taken in order to achieve that purpose. The beginning of 21st century brought the declaration of war on corruption and on the illicit enjoyment of the profits thereof onto the international scene. According to the UN Convention against Transnational Organised Crime (2000), States Parties should adopt the necessary measures to enable the confiscation of proceeds of crime derived from offences (or property of equivalent value) and property, equipment and other instrumentalities used in offences covered by that Convention. The UN Convention against Corruption (2003) states asset recovery explicitly as a fundamental principle and sets forth measures aiming at the direct recovery of property through international cooperation in confiscation. Furthermore, European legislation has made many significant strides forward in less than twenty years concerning money laundering, confiscation, and asset recovery. Crime does not pay, let there be no doubt about it. Nevertheless, we must be very careful not to sing out of tune with individual rights and legal guarantees. On the one hand, innocent individuals and businesses must be protected, since they should not pay for the guilty ones’ faults. On the other hand, the rule of law must be preserved and not be tossed aside regarding those who have carried out criminal activities. An in-depth analysis of judicial decisions on money laundering and confiscation of proceeds of crime issued by European national courts and by the European Court of Human Rights in the last decade has been carried out from a human rights, legal guarantees and criminal law basic principles’ perspective. The undertaken study has revealed the violation of the right to property, of the proportionality principle legal and the infringement of basic principles of states’ domestic substantive and procedural criminal law systems. The most relevant ones have to do with the punishment of money laundering committed through negligence, non-conviction based confiscation and a too-far reaching interpretation of the notion of ‘proceeds of crime’. Almost everything in life has a bright and a dark side. Confiscation of criminal proceeds and asset recovery are not an exception to this rule.

Keywords: confiscation, human rights, money laundering, organized crime

Procedia PDF Downloads 123

Authors: N. R. Putra, A. H. Abdul Aziz, A. S. Zaini, Z. Idham, F. Idrus, M. Z. Bin Zullyadini, M. A. Che Yunus

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The content of omega-3 in soybean oil is important in the development of infants and is an alternative for the omega-3 in fish oils. The investigation of extraction of soybean oil is needed to obtain the bioactive compound in the extract. Supercritical carbon dioxide extraction is modern and green technology to extract herbs and plants to obtain high quality extract due to high diffusivity and solubility of the solvent. The aim of this study was to obtain the optimum condition of soybean oil extraction by modified supercritical carbon dioxide. The soybean oil was extracted by using modified supercritical carbon dioxide (SC-CO₂) under the temperatures of 40, 60, 80 °C, pressures of 150, 250, 350 Bar, and constant flow-rate of 10 g/min as the parameters of extraction processes. An experimental design was performed in order to optimize three important parameters of SC-CO₂ extraction which are pressure (X₁), temperature (X₂) to achieve optimum yields of soybean oil. Box Behnken Design was applied for experimental design. From the optimization process, the optimum condition of extraction of soybean oil was obtained at pressure 338 Bar and temperature 80 °C with oil yield of 2.713 g. Effect of pressure is significant on the extraction of soybean oil by modified supercritical carbon dioxide. Increasing of pressure will increase the oil yield of soybean oil.

Keywords: soybean oil, SC-CO₂ extraction, yield, optimization

Procedia PDF Downloads 235

Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: M. A. Sedghamiz, S. Raeissi

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This study presents three different approaches to estimate bubble point pressures for the binary system of CO2 and ethyl palmitate fatty acid ethyl ester. The first method involves the Peng-Robinson (PR) Equation of State (EoS) with the conventional mixing rule of Van der Waals. The second approach involves the PR EOS together with the Wong Sandler (WS) mixing rule, coupled with the Uniquac Ge model. In order to model the bubble point pressures with this approach, the volume and area parameter for ethyl palmitate were estimated by the Hansen group contribution method. The last method involved the Peng-Robinson, combined with the Wong-Sandler Method, but using NRTL as the GE model. Results using the Van der Waals mixing rule clearly indicated that this method has the largest errors among all three methods, with errors in the range of 3.96–6.22 %. The Pr-Ws-Uniquac method exhibited small errors, with average absolute deviations between 0.95 to 1.97 percent. The Pr-Ws-Nrtl method led to the least errors where average absolute deviations ranged between 0.65-1.7%.

Keywords: bubble pressure, Gibbs excess energy model, mixing rule, CO2 solubility, ethyl palmitate

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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