91 |
Impact du glucomannane de konjac sur les interactions composés volatils - amidon de pomme de terre dans un gel hydraté / Impact of konjac glucomannan on interactions aroma compound - potato starch in a hydrated gelLafarge, Céline 08 December 2016 (has links)
L’objectif de ce travail est de démontrer que la présence de glucomannane de konjac (KGM) dans une matrice d’amidon de pomme de terre permet d’accroître sa stabilité physique sans inhiber l’encapsulation moléculaire de composés d’arôme par l’amylose. Pour cette étude, les deux polyosides choisis sont issus de tubercules de plantes abondantes dans la nature.L’amidon est connu pour interagir avec des composés volatils, soit en les piégeant dans la zone amorphe, soit en formant des complexes d'inclusion. Ce phénomène est appelé encapsulation moléculaire. Cependant, les matrices amylacées à forte teneur en eau présentent une synérèse pouvant être néfaste sur la stabilité du piégeage des composés d’arôme dans le temps. Le KGM possède une capacité à former des solutions extrêmement visqueuses. L’ajout de KGM à faible concentration (0,2 %) à une suspension d’amidon (5 %) perturbe la gélatinisation de l’amidon, accélère la rétrogradation de l’amylose et ralentit la rétrogradation de l’amylopectine. Lors d’un vieillissement accéléré, la présence de KGM assure la stabilité de la suspension d’amidon. Dans une matrice amidon – KGM, l’encapsulation moléculaire du carvacrol par l’amylose a été mise en évidence. Les complexes formés sont de type V6III. Leur formation est dépendante des conditions expérimentales. L’utilisation du propylène glycol favorise la formation de complexes amylose carvacrol. Lors d’un vieillissement accéléré, le KGM assure la stabilité du piégeage du carvacrol.La matrice amidon de pomme de terre – KGM avec un ajout du carvacrol en fin de process présente la stabilité physique du gel et la stabilité du piégeage du carvacrol les plus optimales. / The objective of this study is to demonstrate that the presence of konjac glucomannan (KGM) in a potato starch matrix enhances its physical stability without inhibiting the molecular encapsulation of aroma compounds by amylose. For that purpose, the two selected polysaccharides are from plant tubers, abundant in nature.Starch is known to interact with volatile compounds either by trapping in amorphous phase or by forming inclusion complexes. This phenomenon is called molecular encapsulation. However, at high water content, these starchy matrices exhibit syneresis that can be harmful to the stability of the aroma compounds trapping over time. KGM has the ability to form highly viscous solutions. Our results show that the addition of KGM at low concentration (0.2 %) in starch dispersion (5 %) disrupts the gelatinisation of starch, accelerates the retrogradation of amylose and delays the one of amylopectin. During accelerate aging, the presence of KGM ensures stability of starch suspensions.In starch – KGM matrix, the molecular encapsulation of carvacrol by amylose has been demonstrated. The complexes of caravacrol – amylose are V6III type structure. Their establishment is dependent on experimental conditions. The use of propylene glycol as carrier solvent of carvacrol promotes the formation of complexes between amylose and carvacrol. During accelerate aging, the presence of KGM ensures the stability of carvacrol trapping.The potato starch – KGM matrix with an addition of carvacrol at the end of the process shows the best physical stability of the gel and the best carvacrol trapping.
|
92 |
Microparticules préparées par transacylation entre sérumalbumine humaine et polysaccharides estérifiés : Approche physicochimique, structurelle et fonctionnelle / Microparticles prepared by transacylation between human serum albumin and esterified polysaccharides : physicochemical, structural and functional ApproachesHadef-Djebaili, Imane 18 December 2015 (has links)
Au laboratoire, une méthode originale d'encapsulation par transacylation entre l'alginate de propylène-glycol (PGA) et une protéine a été mise au point. Cette méthode est basée sur la création de liaisons amides entre les fonctions amines libres de la protéine et les groupes esters du PGA dans une phase aqueuse émulsionnée (E/H) après alcalinisation. Les microparticules obtenues, stables, biocompatibles et biodégradables, sont potentiellement intéressantes pour la délivrance de substances actives en thérapeutique ou en cosmétique.Le premier objectif de ce travail est d'étudier l'influence des propriétés physicochimiques des deux biopolymères (protéine et PGA) et de leurs solutions, ainsi que l'effet des paramètres de préparation sur la réaction de transacylation et sur les propriétés des microparticules obtenues. Pour cela, la sérumalbumine humaine (HSA) a servi de protéine modèle et les microparticules ont été préparées dans différentes conditions physicochimiques puis caractérisées. Différents liens ont été établis entre les propriétés physicochimiques des solutions initiales des deux polymères et les propriétés fonctionnelles des microparticules obtenues.Le deuxième objectif est de remplacer le PGA, seul polysaccharide utilisable jusqu'à présent pour la microencapsulation par transacylation, par d'autres polysaccharides naturels, dans la préparation de microparticules. Etant donné ses propriétés intrinsèques limitantes, le remplacement du PGA par d'autres esters polysaccharidiques parait avantageux dans le domaine d'application des microparticules.Dans ce travail, le PGA a été remplacé par une série d'esters semi-synthétiques d'alginate puis par d'autres polysaccharides estérifiés naturels (pectines) ou semi-synthétiques (esters polypectiques et esters de l'acide hyaluronique). Les conditions optimales pour l'utilisation de chaque ester ont été alors déterminées. / In our laboratory, an original method of microencapsulation was developed, based on the use of a transacylation reaction, creating covalent bonds between proteins and propylene glycol alginate (PGA). The covalent bonds are created after alkalization of the aqueous phase of a W/O emulsion, without using bifunctional crosslinking reagent.The resulting microparticles, which are stable, biocompatible and biodegradable, have potential applications for the delivery of active compounds for therapeutics or cosmetics.The first aim of this work is to study the influence of the physicochemical properties of the two polymers (protein and PGA) and of their solutions, as well as the effect of the preparation parameters on the transacylation reaction and on microparticle characteristics. For this purpose, human serum albumin (HSA) was picked as a model protein and microparticles were prepared using several physicochemical conditions then characterized. Several relationships were established between the physicochemical properties of the initial solutions of the two polymers and the functional properties of the resulting microparticles.The second purpose is to replace the PGA, only polysaccharide used for microencapsulation by transacylation so far, by other natural polysaccharides in the preparation of microparticles. Given its limiting intrinsic properties, the replacement of PGA by other polysaccharidic esters seems advantageous in the field of microparticle applications.In this work, the PGA was successfully replaced by a series of semisynthetic alginate esters, and then by other polysaccharidic esters, either natural esters (pectin) or semisynthetic esters (polypectate esters and hyaluronate esters). The optimal conditions for the use of each ester were then determined.
|
93 |
Developement of cycloisomerization reactions for the synthesis of nitrogen or oxygen containing heterocycles / Developement of cycloisomerization reactions for the synthesis of nitrogen or oxygen containing heterocyclesSpina, Rosella 15 December 2011 (has links)
La catalyse, les solvants alternatifs et l'économie d'atome font partie des clés pour le développement de nouvelles stratégies durables de synthèse. Des hétérocycles comme les quinoléines substituées, par réaction de cycloisomérisation catalysée par le cuivre en utilisant les liquides ioniques, et les isoquinoléines carbonylées par réaction de carbonylation oxydante catalysée par le palladium dans le méthanol ont été synthétisées. La formation sélective de 1,3-dihydroisobenzofuranes et/ou 1H-isochromènes a été tentée par réaction de cycloisomérisation catalysée par différent métaux de transition. La synthèse d'hétérocycles à cinq chaînons, par exemple furanes, pyrroles et pyrrolin-4-ones à été mise au point par nouvelle réaction de cycloisomérisation catalysée par de sels de platine ou d'or en utilisant des diols, des amino alcools ou des α-amino-ynones dans le PEG sous activation micro-ondes. Les produits sont récupérés pur après une simple étape de précipitation-filtration. Les α-amino-ynones chiral sont synthétisée à partir de N-protégé carboxyanhydrides des aminoacides (UNCAs). Une réaction de iodocyclisation a été aussi développée pour obtenir de nouvelles structures hétérocycliques. / Catalysis, alternative solvents and atom economy represent key areas for the sustainable development of versatile strategies in organic chemistry. Fused heterocycles, such as substituted quinolines by a cycloisomerization reaction using a recyclable catalytic system copper/ionic liquids and isoquinoline-4-carboxylic esters based on PdI2-catalyzed oxidative carbonylation were prepared. A selective 5-exo-dig or 6-endo-dig cyclization route to obtain 1,3-dihydroisobenzofurans and/or 1H-isochromenes was tested by metal transition cycloisomerization reaction of alkynylbenzyl alcohols in PEG. Five membered ring heterocycles such as furans, pyrroles and pyrrolin-4-ones were successfully obtained by a novel platinum or gold-catalyzed cycloisomerization reaction of diols, aminoalcohols or α-amino-ynones in poly(ethylene glycol) (PEG) under microwave irradiation. The heterocyclic systems were recovered pure after a simple precipitation-filtration work-up. The catalytic systems were studied by using the TEM and XPS techniques. The chiral α-amino-ynone substrates were prepared by an original method starting from N-protected carboxyanhydrides of amino acids (UNCAs). Also unprecedented results are reported in the area of iodocyclization to obtain chiral iodopyrrolin-ones.
|
94 |
Development of new types of mechanocatalytic systems / Développement de nouveaux systèmes enzymatiques mécano-transductifsZahouani, Sarah 25 September 2017 (has links)
Le fascinant processus par lequel les signaux mécaniques sont transformés en réactions biochimiques dans la nature est appelé mécano-transduction. Le but de ma thèse a été de mimer la Nature en élaborant de nouveaux systèmes enzymatiques mécano-transductifs, i.e des matériaux capables de moduler une catalyse enzymatique lorsqu’ils sont sollicités mécaniquement. Nous avons d’abord étudié l’effet de l’étirement sur les chaînes constitutives de films multicouches de polyélectrolytes, matrices souvent utilisées pour le développement de biomatériaux intelligents. Dans le cadre d’une nouvelle stratégie axée sur la modulation mécanique de la conformation, nous avons ensuite élaboré des matrices étirables à base de poly(éthylène glycol)s. Nous avons en particulier développé de tout nouveaux revêtements covalents appelés nanogels qui se sont avérés être déposables sur le silicone étirable et fonctionnalisables avec différentes biomacromolécules, ouvrant ainsi de nouvelles routes biomimétiques. / The fascinating process by which mechanical signals are transformed into biochemical reactions in Nature is called mechanotransduction. The goal of my PhD was to mimic Nature by elaborating new types of mechanocatalytic materials, i.e materials able to modulate a catalytic activity when mechanically stimulated. We first aimed at understanding the impact of stretching on the structural properties of polyelectrolyte multilayers films, polymeric matrices often used for the design of smart biomaterials. Within the framework of a new strategy essentially relying on mechanically induced conformational changes, we then developed stretchable polymeric matrices based on poly(ethylene glycol)s. We more particularly designed new types of covalent coatings, called nanogels. We showed that these architectures were buildable on stretchable silicone and that they could be functionalized with different types of biomacromolecules; thus opening new biomimetic routes.
|
95 |
New grafted PLA-g-PEG polymeric nanoparticles used to improve bioavailability of oral drugsMokhtar, Mohamed 02 1900 (has links)
No description available.
|
96 |
Ethylene glycol rapid methods of detectionBlevins, Lori A. January 1900 (has links)
Master of Veterinary Bioscience / Department of Diagnostic Medicine/Pathobiology / Deon Van Der Merwe / Every year thousands of domestic animals are poisoned by ethylene glycol. Exposure is normally orally, but may be dermal, and poisonings are usually accidental and not malicious. Antifreeze, overwhelmingly the source of the ethylene glycol poisoning, is responsible for over 99% of reported cases. Storage, handling and proper disposal of ethylene glycol is extremely important in limiting access to this deadly product.
Ethylene glycol exposures were involved in 1737 calls made to the American Society for the Prevention of Cruelty to Animals call center between 2006 and 2011. Dogs were involved in approximately 87% of exposures and cats in 13%. There were no seasonal or breed patterns. The most common clinical signs reported were neurological and gastrointestinal for both cats and dogs. Urinary calcium oxalate crystals were reported in 28.6% of exposed cats, and 21% of dogs.
Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) was used to detect calcium oxalate crystals in wax-mounted kidneys from twenty total cases, ten of which were suspected ethylene glycol poisoning submitted to the Kansas State Veterinary Diagnostic Laboratory, and ten samples deemed negative by a pathologist using light microscopy. Pure calcium oxalate monohydrate was used as a reference, and a unique absorption peak was detected between wavenumbers 1290 cm[superscript]-1 and 1320 cm[superscript]-1. The drying of kidney tissues resulted in increased sensitivity for calcium oxalate. Crystal detection by the ATR-FTIR was compared to light microscopy. Bi-fringence of crystals allowed microscopic detection, but the ATR-FTIR specificity for the test was 100%, and sensitivity was 80% compared to traditional microscopy for ca-oxalate crystal identification.
ATR-FTIR was also used to detect un-metabolized ethylene glycol in vomitus using wavenumbers 1084 cm[superscript]−1, 1039 cm[superscript]−1, and 882 cm[superscript]−1, but ethylene glycol was not detectable. Ethylene glycol concentrations in samples were much too low to be detected as ethylene glycol on the ATR-FTIR, as the limit of detection was not distinguishable until 5000 ppm using a serial dilution. These methods presented simple, reliable, quick, sensitive, stable, and highly adaptable tests for detection, diagnosis and treatment of ethylene glycol poisoning.
|
97 |
Laminin-Functionalized Polyethylene Glycol Hydrogels for Nucleus Pulposus RegenerationFrancisco, Aubrey Therese January 2013 (has links)
<p>Intervertebral disc (IVD) disorders and age-related degeneration are believed to contribute to low back pain. There is significant interest in cell-based strategies for regenerating the nucleus pulposus (NP) region of the disc; however, few scaffolds have been evaluated for their ability to promote or maintain an immature NP cell phenotype. Additionally, while cell delivery to the pathological IVD has significant therapeutic potential for enhancing NP regeneration, the development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the NP region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into biomaterial scaffolds for NP tissue engineering or cell delivery to the disc may be beneficial for promoting NP cell survival and phenotype. In this dissertation, laminin-111 (LM111) functionalized poly(ethylene glycol) (PEG) hydrogels were developed and evaluated as biomaterial scaffolds for cell-based NP regeneration. </p><p>Here, PEG-LM111 conjugates with functional acrylate groups for crosslinking were synthesized and characterized to allow for protein coupling to both photocrosslinkable and injectable PEG-based biomaterial scaffolds. PEG-LM111 conjugates synthesized using low ratios of PEG to LM111 were found support NP cell attachment and signaling in a manner similar to unmodified LM111. A single PEG-LM111 conjugate was conjugated to photocrosslinkable PEG-LM111 hydrogels, and studies were performed to evaluate the effects of hydrogel formulation on immature NP cell phenotype in vitro. When primary immature porcine NP cells were seeded onto PEG-LM111 hydrogels of varying stiffnesses, softer LM111 presenting hydrogels were found to promote cell clustering and increased levels of sGAG production as compared to stiffer LM111 presenting and PEG-only gels. When cells were encapsulated in 3D gels, hydrogel formulation was found to influence NP cell metabolism and expression of proposed NP phenotypic markers, with higher expression of N-cadherin and cytokeratin 8 observed for cells cultured in softer (<1 kPa) PEG-LM111 hydrogels. </p><p>A novel, injectable PEG-LM111 hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. PEG-LM111 conjugates were crosslinked via a Michael-type addition reaction upon the addition of PEG-octoacrylate and PEG-dithiol. Injectable PEG-LM111 hydrogel gelation time, mechanical properties, and ability to retain delivered cells in the IVD space were evaluated. Gelation occurred in approximately 20 minutes without an initiator, with dynamic shear moduli in the range of 0.9 - 1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 hydrogel carrier, as compared to cells in liquid suspension. </p><p>The studies presented in this dissertation demonstrate that soft, LM111 functionalized hydrogels may promote or maintain the expression of specific markers and cell-cell interactions characteristic of an immature NP cell phenotype. Furthermore, these findings suggest that this novel, injectable laminin-functionalized biomaterial may be an easy to use and biocompatible carrier for delivering cells to the IVD.</p> / Dissertation
|
98 |
A non-syn-gas catalytic route to methanol productionWu, Cheng-Tar January 2013 (has links)
At present, more than 80% of the world’s energy consumption and production of chemicals is originated from the use of fossil resources. There is a tremendous growing interest in utilising biomass molecules for energy provision due to their carbon neutrality. Lower alcohols such as methanol and ethanol if produced from biomass as transportation fuels as well as platform chemicals, can become strategically important for many energy/chemically starved countries. Currently, they are synthesised by indirect and inefficient processes. We show for the first time in this thesis study that ethylene glycol, the simplest representative of biomass-derived polyols, can be directly converted to these two lower alcohols by selective hydrogenolysis over modified Raney Ni and Cu catalysts in hydrogen atmosphere. This work provides essential information that may lead to the development of new catalysts for carbohydrate activation to methanol, a novel but important reaction concerning the important biomass conversion to transportable form of energy. Modification of electronic structure and the adsorption properties of Raney catalysts have therefore been achieved by blending with second metal(s). It is found that the activity and selectivity of this reaction can be significantly affected by this approach. In contrast, there is no subtle effect on methanol selectivity despite a great variation in the d-band centre positions of metal catalysts which show a distinctive effect on other products. Our result suggests that methanol is produced on specific surface sites independent from the other sites at an intrinsic rate and will not be converted to other products by the d-band alteration. On the other hand, it is reported in this thesis that a dramatic improvement in the combined selectivity to methanol/ethanol reaching 80% can be obtained over a Pd/Fe<sub>3</sub>O<sub>4</sub> catalyst under relatively milder conditions (20 bar and 195 oC). This direct production of the non-enzymatic bio-alcohols is established over a carefully prepared co-precipitated Pd/Fe<sub>3</sub>O<sub>4</sub> catalyst which gives a metallic phase of unexpectedly high dispersion ranging from small clusters to individual metal adatoms on defective iron oxide to give the required metal-support interaction for the novel synthesis. It is demonstrated that the small PdFe clusters on iron oxide surface provide the active species responsible for methanol production. In addition, a related Rh/Fe<sub>3</sub>O<sub>4</sub> catalyst synthesised by co-precipitation is also shown to be selective for CO<sub>2</sub> and H<sub>2</sub> production from a direct methane-oxygen oxidation reaction. As a result, 2.7% conversion of methane with selectivity ratio of CO<sub>2</sub>/H<sub>2</sub> = 4 in a mixed gas feed stream of CH<sub>2</sub>/O<sub>2</sub> = 30 at 300 <sup>o</sup>C is obtained. The reaction is operated in a kinetically controlled regime at 300<sup>o</sup>C, where the CO formation from reverse water gas shift reaction is greatly suppressed. It is evident that the Rh/Fe<sub>3</sub>O<sub>4</sub> acts as an interesting bifunctional catalyst for this reaction. This catalyst firstly gives a high dispersion of Rh which is expected to deliver a higher surface energy with enhanced activity. The Rh metal surface provides catalytically active sites for dissociation of methane to adsorbed hydrogen and carbon atoms effectively, and active oxygen on metal surface readily catalyses the carbon atoms to CO. Following these elementary reactions, the surface oxygen from Fe<sub>3</sub>O<sub>4</sub> subsequently converts it to CO<sub>2</sub> selectively at the metal-support interface. As a result, the novel study of catalytic biomass conversion and the discoveries of new catalysts are reported in this thesis.
|
99 |
Φαρμακοδυναμική μελέτη συνθετικού αντικαρκινικού πεπτιδίου και βελτίωση της in vivo σταθερότητας με σύνδεση με πολυαιθυλενογλυκόληΜπαμπούρη, Ιωάννα 06 February 2014 (has links)
Η συσχέτιση της πρωτεΐνης PSP94 με τον καρκίνο του προστάτη είναι γνωστή, καθώς μειωμένα επίπεδα της PSP94 σχετίζονται με τα προχωρημένα, μεταστατικά στάδια καρκίνου του προστάτη, και υποτίθεται ότι η πλήρης έκφρασή της συμβάλλει στην αναχαίτιση της καρκινικής ανάπτυξης. Το PCK3145, ένα συνθετικό δεκαπενταμερές πεπτίδιο, του οποίου η αλληλουχία αμινοξέων είναι ταυτόσημο με την αλληλουχία των αμινοξέων 31 έως 45 της PSP94, επιλέχτηκε μεταξύ 12 διαφορετικών πεπτιδίων που προέκυψαν από την PSP94 καθώς εδείχθη οτι ανακεφαλαιώνει in vitro και in vivo τις λειτουργίες και ιδιότητες της PSP94, και άρα είναι ένα μόριο που μπορεί να χρησιμοποιηθεί στην καταστολή της ανάπτυξης του καρκίνου του προστάτη. Ωστόσο, φαρμακοκινητικές μελέτες σε ζώα και ασθενείς με καρκίνο του προστάτη, κατέδειξαν ταχεία κάθαρση και μικρό χρόνο ημιζωής. Προκειμένου να ενισχυθεί το φαρμακοκινητικό προφίλ του πεπτιδίου PCK3145 και ως εκ τούτου να βελτιωθεί η φαρμακοδυναμική του, υπέστη χημική τροποποίηση με προσθήκη πολυαιθυλενικής γλυκόλης (PEG). Η πειραματική εργασία παρουσιάζει τα αποτελέσματα μιας συστηματικής μελέτης σχετικά με την επίδραση της πεγκυλίωσης στο PCK3145 συγκρίνοντας την πρωτεολυτική σταθερότητα και βιολογική δράση δύο πεγκυλιωμένων συζευγμάτων του με την καθαρή μορφή του.
Για την ποσοτικοποίηση και για τα πειράματα σταθερότητας χρησιμοποιήθηκε ένα σύστημα υγρής χρωματογραφίας υψηλής απόδοσης HPLC αποτελούμενο από μια αντλία Ultimate (Dionex). Ο χρωματογραφικός διαχωρισμός επιτεύχθηκε με μια στήλη ανάστροφης φάσης C18. Επετεύχθη για πρώτη φορά η ανάπτυξη αναλυτικής μεθοδολογίας HPLC για τον προσδιορισμό των πεγκυλιωμένων αναλόγων με υψηλού βαθμού γραμμικότητα, ειδικότητα, επαναληψιμότητα και αναπαραγωγιμότητα. Η πρωτεολυτική σταθερότητα των συζευγμάτων PEG σε ανθρώπινο πλάσμα προσδιορίστηκε με χρήση υγρής χρωματογραφίας HPLC και αποκαλύφθηκε μείωση του ποσοστού αποδόμησης και ενίσχυσξ της σταθερότητας του πεπτιδικών μορίων σε ανθρώπινο πλάσμα.
H μελέτη επιβίωσης της κυτταρικής σειράς καρκίνου του προστάτη PC3 μετά την προσθήκη των πεπτιδικών μορίων υπό μελέτη υπολογίστηκε με τις μεθόδους ΜΤΤ και Trypan blue. 50% αναστολή της κυτταρικής αύξησης/μεταβολισμού επετεύχθη με τις συγκεντρώσεις των 10μg/ml και για τα τρία πεπτίδια. Ωστόσο, τα πεγκυλιωμένα ανάλογα επέφεραν ισχυρότερη ανασταλτική επίδραση στην κυτταρική αύξηση σε μικρότερες δόσεις. Παρόμοια ενθαρρυντικά αποτελέσματα υπήρξαν και για την δράση των μορίων στη καρκινική σειρά του μαστού MCF-7. Τα αποτελέσματα της μελέτης συνοψίζονται στην ικανότητα της πεγκυλίωσης να βελτιώνει τη σταθερότητα του PCK3145 και έτσι να ενισχύει τη βιολογική του δράση. Μελλοντικά πειράματα θα αποσαφηνίσουν περισσότερο τόσο την δράση των μορίων σε καρκινικές σειρές πέραν του προστάτη αλλά και την φαρμακοκινητική συμπεριφορά των πεπτιδικών αναλόγων μέσω πειραμάτων in vivo της βιοκατανομής και μεταβολισμού τους. / PSP94, protein is known to have specific implications with prostate cancer where a down-regulation of PSP94 levels is associated with advanced metastatic prostate cancer and it is supposed that the full expression contributes to the inhibition of tumor growth. PCK3145 is a synthetic 15-mer peptide that matches the natural sequence of amino acids 31 to 45 of PSP94 and was selected from 12 other peptides derived from PSP94 as it exhibited the best in vitro and animal in vivo properties similar to PSP94. Thus, it is a molecule hat can be used to suppress the growth of prostate cancer.However pharmacokinetics studies in animals and in patients with prostate cancer showed rapid clearance and a short half-life. In order to alter the pharmacokinetic profile of the peptide, and thereby to improve its pharmacodynamic potential PCK3145 was chemically modified with polyethylene glycol (PEG).This experimental work presents the results of a systematic study on the influence of the PEGylation of PCK3145 peptides on the proteolytic stability and biological activity of these conjugates compared to the wild-type peptide.
For the quantification and stability assays an HPLC system was used consisted of an Ultimate 3000 Pump (Dionex). Chromatographic separation was achieved on RP, C18 column. An HPLC method development for the determination of the PEG-peptide conjugates was assessed for the first time. A high degree of linearity, specificity as well as repeatability and reproducibility were also achieved. The proteolytic stability of the PEG-peptide conjugates in human plasma was assessed by HPLC chromatography, which revealed a significant decrease in the degradation.
Proliferation of PC3 cancer cell line was measured using the MTT and Trypan blue test. A 50% inhibition of the cell metabolism/growth was achieved by the concentrations of 10 μg/ml of the three peptides. However, at lower concentrations stronger growth inhibitory effect was observed for the PEG-peptides. Similar encouraging results have also seen for the action of molecules in cancer cell lines MCF-7.The results of this study emphasize the ability of PEGylation to improve the stability of PCK3145 and thus to enhance the biological activity. Future experiments willi clarify more the action of molecules in cancer cell lines beyond the prostate and the pharmacokinetic behavour of peptide analogs through in vivo experiments of biodistribution and metabolism.
|
100 |
Water transport study in crosslinked poly(ethylene oxide) hydrogels as fouling-resistant membrane coating materialsJu, Hao 15 September 2010 (has links)
The major objective of this research is a systematic experimental exploration of hydrophilic materials that can be applied as coating materials for conventional ultrafiltration (UF) membranes to improve their fouling resistance against organic components. This objective is achieved by developing new, fouling-reducing membrane coatings and applying these coatings to conventional UF membranes, which can provide unprecedented reduction in membrane fouling and marked improvements in membrane lifetime.
Novel polymeric materials are synthesized via free-radical photopolymerization of mixtures containing poly(ethylene glycol) diacrylate (PEGDA), photoinitiator, and water. PEGDA chain length (n=10-45, where n is the average number of ethylene oxide units in the PEGDA molecule) and water content in the prepolymerization mixture (0-80 wt.%) were varied. Crosslinked PEGDA (XLPEGDA) exhibited high water permeability and good fouling resistance to oil/water mixtures. Water permeability increased strongly with increasing the water content in the prepolymerization mixture. Specifically, for XLPEGDA prepared with PEGDA (n=13), water permeability increased from 0.6 to 150 L um/(m2 h bar) as prepolymerization water content increased from 0 to 80 wt.%. Water permeability also increased with increasing PEGDA chain length. Moreover, water permeability exhibits a strong correlation with equilibrium water uptake. However, solute rejection, probed using poly(ethylene glycol)s of well defined molar mass, decreased with increasing prepolymerization water content and increasing PEGDA chain length. That is, there is a tradeoff between water permeability and separation properties: Materials with high water permeability typically exhibit low solute rejections, and vice versa.
The fouling resistance of XLPEGDA materials was characterized via contact angle measurements and static protein adhesion experiments. From these results, XLPEGDA surfaces are more hydrophilic in samples prepared at higher prepolymerization water content or with longer PEGDA chains, and the more hydrophilic surfaces generally exhibit less BSA accumulation. These materials were applied to polysulfone (PSF) UF membranes to form coatings on the surface of the PSF membranes. Oil/water crossflow filtration experiments showed that the coated PSF membranes had water flux values 400% higher than that of an uncoated PSF membrane after 24 h of operation, and the coated membranes had higher organic rejection than the uncoated membranes. / text
|
Page generated in 0.0264 seconds