L’imagerie médicale a longtemps été limitée à cause des performances médiocres des fluorophores organiques. Récemment la recherche sur les nanocristaux semi-conducteurs a grandement contribué à l’élargissement de la gamme d’applications de la luminescence dans les domaines de l’imagerie et du diagnostic. Les points quantiques (QDs) sont des nanocristaux de taille similaire aux protéines (2-10 nm) dont la longueur d’onde d’émission dépend de leur taille et de leur composition. Le fait que leur surface peut être fonctionnalisée facilement avec des biomolécules rend leur application particulièrement attrayante dans le milieu biologique. Des QDs de structure « coeur-coquille » ont été synthétisés selon nos besoins en longueur d’onde d’émission. Dans un premier article nous avons modifié la surface des QDs avec des petites molécules bi-fonctionnelles portant des groupes amines, carboxyles ou zwitterions. L’effet de la charge a été analysé sur le mode d’entrée des QDs dans deux types cellulaires. À l’aide d’inhibiteurs pharmacologiques spécifiques à certains modes d’internalisation, nous avons déterminé le mode d’internalisation prédominant. L’endocytose par les radeaux lipidiques représente le mode d’entrée le plus employé pour ces QDs de tailles similaires. D’autres modes participent également, mais à des degrés moindres. Des disparités dans les modes d’entrée ont été observées selon le ligand de surface. Nous avons ensuite analysé l’effet de l’agglomération de différents QDs sur leur internalisation dans des cellules microgliales. La caractérisation des agglomérats dans le milieu de culture cellulaire a été faite par la technique de fractionnement par couplage flux-force (AF4) associé à un détecteur de diffusion de la lumière. En fonction du ligand de surface et de la présence ou non de protéines du sérum, chacun des types de QDs se sont agglomérés de façon différente. À l'aide d’inhibiteur des modes d’internalisation, nous avons corrélé les données de tailles d’agglomérats avec leur mode d’entrée cellulaire. Les cellules microgliales sont les cellules immunitaires du système nerveux central (CNS). Elles répondent aux blessures ou à la présence d’inflammagènes en relâchant des cytokines pro-inflammatoires. Une inflammation non contrôlée du CNS peut conduire à la neurodégénérescence neuronale et est souvent observée dans les cas de maladies chroniques. Nous nous sommes intéressés au développement d’un nanosenseur pour mesurer des biomarqueurs du début de l’inflammation. Les méthodes classiques pour étudier l’inflammation consistent à mesurer le niveau de protéines ou molécules relâchées par les cellules stressées (par exemple monoxyde d’azote, IL-1β). Bien que précises, ces méthodes ne mesurent qu’indirectement l’activité de la caspase-1, responsable de la libération du l’IL-1β. De plus ces méthode ne peuvent pas être utilisées avec des cellules vivantes. Nous avons construit un nanosenseur basé sur le FRET entre un QD et un fluorophore organique reliés entre eux par un peptide qui est spécifiquement clivé par la caspase-1. Pour induire l’inflammation, nous avons utilisé des molécules de lipopolysaccharides (LPS). La molécule de LPS est amphiphile. Dans l’eau le LPS forme des nanoparticules, avec des régions hydrophobes à l’intérieure. Nous avons incorporé des QDs dans ces régions ce qui nous a permis de suivre le cheminement du LPS dans les cellules microgliales. Les LPS-QDs sont internalisés spécifiquement par les récepteurs TLR-4 à la surface des microglies. Le nanosenseur s’est montré fonctionnel dans la détermination de l’activité de la caspase-1 dans cellules microgliales activées par le LPS. Éventuellement, le senseur permettrait d’observer en temps réel l’effet de thérapies ciblant l’inflammation, sur l’activité de la caspase-1. / Medical imaging based on fluorescence has suffered from the poor photostability and mediocre performance of organic fluorophores. The discovery and subsequent improvements in nanocrystal synthesis and functionalization has greatly benefited the applications in medical imaging and the development of nanocrystal-based sensors for diagnostics. QDs are semi-conductor nanocrystals which have similar sizes as proteins (2-10 nm). They are highly luminescent, and can be made to emit at any desired wavelength by varying their size and composition. The surface of QDs can be easily functionalized with biomolecules. Hence, it is interesting to study how QDs interact in the biological world. Highly luminescent core-shell QDs emitting at different wavelengths were prepared according to our needs. In a first study, the surface of the QDs was modified with various small bi-functional thiolated ligands (carboxylated, aminated and zwitterionic). The modified-QDs of nearly identical sizes were administered in vitro to study the impact of surface charge and cell type on the mode and extent of cell uptake and elimination. Using specific inhibitors of cell uptake we determined which modes contributed to the internalization of the QDs. Endocytosis mediated by lipid rafts represented the predominant pathway for the internalization of QDs. However, other modes contributed to a lesser degree, depending on the surface ligand. We then analyzed the effect of QD agglomeration in cell culture media on its cellular uptake by microglia. Thorough characterization of QD agglomerate size distribution was conducted by asymmetrical flow field-flow fractionation (AF4) with a dynamic light scattering detector. Depending on the type of surface ligand and if serum proteins were present, the agglomeration pattern of the QDs was significantly different. With inhibitors of specific modes of cell uptake, we showed that the size distribution data, obtained by AF4, correlated with the modes of cell uptake. Microglia cells are immune cells of the central nervous system (CNS). They respond to injury or the presence of inflammagens by producing pro-inflammatory cytokine. Inflammation in the CNS may lead to loss of neurons, and can found in many chronic diseases. We were interested in building nanosensors to measure the onset of inflammation. Current methods to study inflammation consist in measuring levels of certain proteins or chemicals released by stressed cell (e.g. Western blot or ELISA assay for IL-1β). Although precise, these methods measure indirectly the activity of the enzyme responsible for releasing IL-1β, i.e. caspase-1. Moreover, these methods cannot be applied to live cells. We designed a sensor based on FRET between a QD and a dye linked by a peptide specifically cleaved by the caspase-1. To induce inflammation, we applied lipopolysaccharides (LPS), which are endotoxins present in Gram negative bacteria responsible for sceptic shock. The LPS form nanoparticles due to their amphiphilicity. The interior hydrophobic regions were used to load hydrophobic QDs, making the LPS luminescent. The microglia internalized LPS-QD predominantly through TLR-4 membrane receptors. We describe how the LPS induce inflammation and demonstrated the functionality of the QD-based sensor. Eventually, the sensor could be used to monitor in real time the action of therapeutics against inflammation.

A study was conducted to evaluate the properties and processes influencing the rate and magnitude of volume decrease and strength gain for oil sand fine tailings resulting from a change in bitumen extraction process (caustic versus non-caustic) and the effect of adding a coagulant to caustic fine tailings. Laboratory flume deposition tests were carried out with the objective to hydraulically deposit oil sand tailings and compare the effects of extraction processes on the nature of beach deposits in terms of geometry, particle size distribution, and density. A good correlation exists between flume deposition tests results using oil sand tailings and the various other tailings materials. These comparisons show the reliability and effectiveness of flume deposition tests in terms of establishing general relationships and can serve as a guide to predict beach slopes. Fine tailings were collected from the various flume tests and a comprehensive description of physical and chemical characteristics of the different fine tailings was carried out. The characteristics of the fine tailings is presented in terms of index properties, mineralogy, specific surface area, water chemistry, liquid limits, particle size distribution and structure. The influence of these fundamental properties on the compressibility, hydraulic conductivity and shear strength properties of the fine tailings was assessed. Fourteen two meter and one meter high standpipe tests were instrumented to monitor the rate and magnitude of self-weight consolidation of the different fine tailings materials. Consolidation tests using slurry consolidometers were carried out to determine consolidation properties, namely compressibility and hydraulic conductivity, as well as the effect of adding a coagulant (calcium sulphate [CaSO4]) to caustic fine tailings. The thixotropic strength of the fine tailings was examined by measuring shear strength over time using a vane shear apparatus. A difference in water chemistry during bitumen extraction was concluded to be the cause of substantial differences in particle size distributions and degree of dispersion of the comparable caustic and non-caustic fine tailings. The degree of dispersion was consistent with predictions for dispersed clays established by the sodium adsorption ratio (SAR) values for these materials. The biggest advantage of non-caustic fine tailings and treating caustic fine tailings with coagulant is an increased initial settlement rate and slightly increased hydraulic conductivity at higher void ratios. Thereafter, compressibility and hydraulic conductivity are governed by effective stress. The chemical characteristics of fine tailings (water chemistry, degree of dispersion) do not have a significant impact on their compressibility behaviour and have only a small influence at high void ratio (low effective stress). Fine tailings from a caustic based extraction process had relatively higher shear strengths than comparable non-caustic fine tailings at equivalent void ratios. However, shear strength differences were small and the overall impact on consolidation behaviour, which also depends on compressibility and hydraulic conductivity, is not expected to be significant.

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)

科学研究費補助金 研究種目:一般研究(C) 課題番号:60580177 研究代表者:飯田 孝夫 研究期間:1985-1986年度

No description available.

A non-reactive model system comprising a highly concentrated and unstable oil-in-water emulsion was used to investigate the retention of oil by the membrane in producing biodiesel with a membrane reactor. Critical flux was identified using the relationship between the permeate flux and transmembrane pressure along with the separation efficiency of the membrane. It was shown that separation efficiencies above 99.5% could be obtained at all operating conditions up to the critical flux. It was observed that the concentration of oil in all collected permeate samples using the oil-water system was below 0.2 wt% when operating at a flux below the critical flux. Studies to date have been limited to the characterization of low concentrated emulsions below 15 vol.%. The average oil droplet size in highly concentrated emulsions was measured as 3200 nm employing direct light scattering (DLS) measurement methods. It was observed that the estimated cake layer thickness of 20 to 80 mm was larger than external diameter of the membrane tube i.e. 6 mm based on a large particle size. Settling of the concentrated emulsion permitted the detection of a smaller particle size distribution (30-100 nm) within the larger particles averaging 3200 nm. It was identified that DLS methods could not efficiently give the droplet size distribution of the oil in the emulsion since large particles interfered with the detection of smaller particles. The content of the smaller particles represented 1% of the total weight of oil at 30°C and 5% at 70°C. This was too low to be detected using DLS measurements but was sufficient to affect ultrafiltration. In order to study the critical flux in the presence of transesterification reaction and the effect of cross flow velocity on separation, various oils were transesterified in another membrane reactor providing higher cross flow velocity. higher cross flow velocity provides better separation by reducing materials deposition on the surface of the membrane due to higher shearing. The oils tested were canola, corn, sunflower and unrefined soy oils (Free Fatty Acids (FFA< 1%)), and waste cooking oil (FFA= 9%). The quality of all biodiesel samples was studied in terms of glycerine, mono-glyceride, di-glyceride and tri-glyceride concentrations. The composition of all biodiesel samples were in the range required by ASTM D6751 and EN 14214 standards. A critical flux based on operating pressure in the reactor was reached for waste cooking and pre-treated corn oils. It was identified that the reaction residence time in the reactor was an extremely important design parameter affecting the operating pressure in the reactor. / Natural Sciences and Engineering Research Council of Canada (NSERC)

Marine aerosols have attracted increasing attention over the past 15 years because of their potential significance for global climate modelling. The size distribution of these aerosols extends from super-micrometer sea salt mode particles down through 150 nm accumulation mode particles, 40 nm Aitken mode particles and nucleation mode particles which extend from 25 nm right down to clusters of a few molecules. The process by which the submicrometer modes form and grow and their composition have remained topics of debate throughout this time in large part because of the difficulties associated with determining their composition and relating it to proposed models of the formation process. The work compared the modality of marine aerosol influencing the South-east-Queensland region with that of other environmental aerosols in the region. The aerosol was found to be consistent with marine aerosols observed elsewhere with concentrations below 1000 cm-3 and frequently exhibiting the distinct bimodal structure associated with cloud processing, consisting of an Aitken mode at approximately 40 nm, an accumulation mode in the range 100-200 nm and a coarse mode attributed to sea salt between 600 and 1200 nm. This work included the development of two new techniques for aerosol research. The first technique measures aerosol density using a combination of aerosol size distribution and gravimetric mass concentration measurements. This technique was used to measure the density of a number of submicrometer aerosols including laboratory generated NaCl aerosol and ambient aerosol. The densities for the laboratory generated aerosols were found to be similar to those for the bulk materials used to produce them. The technique, extended to super-micrometer particle size range may find application in ambient aerosol research where it could be used to discriminate between periods when the aerosol is dominated by NaCl and periods when the density is more representative of crustal material or sulfates. The technique may also prove useful in laboratory or industrial settings for investigating particle density or in case where the composition is known, morphology and porosity. The second technique developed, integrates the existing physicochemical techniques of volatilisation and hygroscopic growth analysis to investigate particle composition in terms of both the volatilisation temperatures of the chemical constituents and their contribution to particle hygroscopic behaviour. The resulting volatilisation and humidification tandem differential mobility analyser or VH-TDMA, has proven to be a valuable research tool which is being used in ongoing research. Findings of investigations relating the composition of the submicrometer marine aerosol modes to candidate models for their formation are presented. Sea salt was not found in the numerically dominant particle type in coastal nucleation mode or marine Aitken and accumulation modes examined on the Southeast Queensland coast during periods where back trajectories indicated marine origin. The work suggests that all three submicrometer modes contain the same four volatile chemical species and an insoluble non-volatile residue. The volatility and hygroscopic behaviours of the particles are consistent with a composition consisting of a core composed of sulfuric acid, ammonium sulfate and an iodine oxide coated with a volatile organic compound. The volume fraction of the sulfuric acid like species in the particles shows a strong dependence on particle size.

La biomasse lignocellulosique comprend les sous-produits agricoles et industriels pouvant être utilisés comme matière première dans des bioprocédés variés destinés à produire des molécules d'intérêt énergétique ou chimique. Ces ressources lignocellulosiques, peuvent notamment être fournies par l'industrie papetière qui est particulièrement adaptée pour les bio-raffineries modernes car elle est en capacité de produire en grande quantité un substrat ayant une faible teneur en lignine et sans composés inhibiteurs. La bagasse de canne à sucre est également un substrat prometteur par sa composition chimique simple et son abondance dans les pays tropicaux. Lors de l'utilisation de ces substrats, l'hydrolyse enzymatique constitue une étape cruciale permettant la transformation des fibres de cellulose en une source de carbone fermentescible. Si les aspects biochimiques de cette étape d'hydrolyse font l'objet de nombreuses recherches et de développements, les réactions sous haute teneur en matière sèche font apparaître des limitations physiques qui sont beaucoup moins étudiées et analysées mais constituent des verrous scientifiques et technologiques qui freinent actuellement l'utilisation de cette ressource abondante et durable. Ce travail s'inscrit dans ce contexte et propose l'étude de cette étape d'hydrolyse enzymatique de la lignocellulose en s'intéressant conjointement aux aspects biochimiques et physiques de façon à aller vers une compréhension et une maîtrise des transferts (de masse, de chaleur) dans les réactions à forte concentration en substrat. La stratégie adoptée a consisté à réaliser et analyser des réactions d'hydrolyse sous différentes conditions opératoires en travaillant dans un premier temps sur des concentrations intermédiaires (suspension semi-diluée), c'est-à-dire en introduisant, mais de façon limitée, les complexités dues aux interactions entre particules/fibres de lignocellulose. Les résultats obtenus sont ensuite utilisés pour élaborer une stratégie adaptée aux fortes concentrations. Les aspects physiques analysés sont essentiellement le comportement rhéologique du milieu réactionnel ainsi que la morpho-granulométrie des objets en suspension. Différentes métrologies, tant in-situ que ex-situ, ont été mises en œuvre et apportent des résultats complémentaires. Les études ont été menées sur un substrat de référence, le papier Whatman, et deux substrats à vocation industrielle: la pâte à papier et la bagasse de canne à sucre. La stratégie d'étude porte sur les aspects suivants: (i) le suivi de l'évolution des comportements rhéologiques et des propriétés morphologiques des suspensions au cours de l'hydrolyse, (ii) l'étude des mécanismes d'hydrolyse lors de la dégradation des substrats, (iii) l'étude de l'impact de la composition et de la structure des substrats sur les cinétiques de solubilisation et d'hydrolyse, (iv) la quantification de la contribution des différentes activités enzymatiques, seules ou en mélange par une approche physique multi-échelle et (v) le contrôle et l'optimisation des conditions d'alimentation dans un procédé discontinu alimenté (fed-batch) afin d'atteindre des conditions de milieu concentré. Les chapitres 1 et 2 de ce document sont consacrés à une étude bibliographique du sujet et à la présentation des matériels et méthodes mis en œuvre. Le troisième chapitre présente les résultats obtenus et leur analyse. Il est constitué de trois sections: tout d'abord une étude des propriétés des différents enzymes ou cocktail d'enzymes utilisés, des substrats retenus et des suspensions avec, notamment, la détermination des régimes semi-dilués et concentrés. Ensuite sont présentées et analysées les hydrolyses effectuées en milieu semi-dilué. Les mécanismes d'hydrolyse (fragmentation, solubilisation, hydratation et séparation des agglomérats) sont étudiés pour diverses concentrations et divers enzymes/cocktails. Enfin les résultats en milieu concentré sont présentés dans une dernière section. / Lignocellulosic biomass consists of several agriculture and industrial by-products that can be used as raw material for several bioprocesses to obtain range of products. Among lignocellulosic sources, the pulp & paper industry is appropriated for modern bio-refining thank to pulp with low lignin content and free of inhibitory compounds. Besides, sugarcane bagasse is a very promising feedstock because of its simple chemical composition and its abundancy especially in tropical countries. In the bioconversion of lignocellulose, enzymatic hydrolysis is a crucial step that allows the transformation of cellulosic and hemicellulosic fibers into fermentable carbon sources. The lack of knowledge about physical limitations and hydrolysis mechanisms, especially at high dry matter content, stands as the main barrier which forbids the scale-up of bio-refinery processes. Thus, the efficient and sustainable use of lignocellulosic resources is currently a major challenge and need to be investigated. In this context, this PhD focused on the enzymatic hydrolysis of lignocellulose by both physical and biochemical approaches. The strategy consisted in carrying out and in analyzing the hydrolysis reactions under different operating conditions with semi-dilute suspensions. Then, obtained results were used to develop a hydrolysis strategy for concentrated suspensions. Different methodologies, in- and ex-situ analyses, were implemented and provided complementary results. From physical approach, analyses consisted in rheological behavior of suspensions as well as the morpho-granulometry of particles. The study was carried out on a reference substrate, Whatman paper, and on two industrial substrates, paper pulp and sugarcane bagasse. The strategy aimed to investigate different stakes: (i) evolution of rheological behaviors and the morphological properties of suspensions, (ii) hydrolysis mechanisms during the degradation of substrates, (iii) impact of substrate composition and structure on solubilization and hydrolysis kinetics, (iv) quantification of the contribution of single enzyme and enzyme mixture activities by multi-scale physical approaches and (v) control and optimization of feeding parameters for fed-batch process in order to access to concentrated suspension. Chapters 1 and 2 of this document are devoted to a research bibliographic and presentation of materials and methods. The third chapter presents obtained results and discussion in three sections. The first one is a study of the properties of different enzymes and substrates, in particular, the determination of semi-dilute and concentrated regime. Subsequently the enzymatic hydrolysis at semi-dilute regime is presented to highlight the hydrolysis mechanisms (fragmentation, solubilization, solvation and agglomerate separation) in relationship with enzyme mixtures and dosages. Finally, results in concentrated regime are discussed in the final section.

CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Tereza Pokorná Title of Diploma thesis Terbinafine-loaded biodegradable polymeric systems for topical administration Supervisor: PharmDr. Eva Šnejdrová, Ph.D. In the diploma thesis the released properties of solid dispersions with terbinafine, based on polyesters of D,L-lactic acid and glycol acid, branched with pentaerythritol and tripentaerythritol are studied. The theoretical part deals with solid dispersions, their classification and methods of preparation, methods of drug dissolution testing, properties, effect, use of terbinafine and preparations containing terbinafine. In the experimental part, solid dispersions were prepared by the melting method. The drug was incorporated into the polyester in the form of a hydrochloride or a base in a concentration of 10 % or 20 %. Some systems were plasticized with 30% triethyl citrate. Thin layers were formulated from solid dispersions, and drug dissolution tests were performed on phosphate buffer pH 7.4 at 37 řC. Assay of terbinafine released was performed spectrophotometrically at 223 nm and ultra-high performance liquid chromatography. Based on the results of this diploma thesis, it can be clearly stated that the suitable carrier of terbinafine...