Дисертації з теми "Amidoamine"
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1
Martello, F. "Poly(amidoamine)s of biotechnological interest." Doctoral thesis, Università degli Studi di Milano, 2008. http://hdl.handle.net/2434/59949.
Анотація:
Abstract:
Poly(amidoamine)s (PAAs) represent a promising material for drug delivery applications. They are synthetic functional polymers endowed with a combination of properties making them suitable for a variety of biomedical applications mostly related to drug delivery systems. PAAs can be obtained by stepwise polyaddition of primary or secondary aliphatic amines to bisacrylamides. The synthesis is carried out in water or protic solvent, with a mild base and at room temperature.
In the first section of this thesis, a group of novel amphoteric PAAs homo- and copolymers containing secondary and tertiary amine groups in their main chain and different structures in the bisacrylamide segments were synthesized and evaluated as magnetic nanoparticles coating agents.
In the second section of this thesis, a general method for preparing linear high polymers of peptides was investigated. Polymers with an average molecular weight included in the range 3000 – 40000 were obtained by Michael polyaddition reaction between 2,2-bisacrylamidoacetic acid or N,N’-bisacryloylpiperazine and glutathione (reduced and oxidised) or the RGD peptide. In preliminary biological tests these polymers showed a good values of zeta potential and negligible values of cytotoxicity and haemolytic activity. Further in vitro tests are in progress to investigate the biological properties of these polymers in comparison with the parent peptides.
In the third section of this thesis, gene delivery properties of new hyperbranched PAAs, containing disulfide linkages in the main chain, were investigated in comparison with the relevant linear polymers. Structural characterization of the polymers synthesized and the reactivity of the monomers utilized were also determined. The results shown by these polymers in DNA transfection are very promising and encourage further studies in vitro with these biodegradable hyperbranched PAAs to test the effect, on transfection efficiency, of different terminal groups.
2
Richter-Egger, Dana L. "Spectroscopic investigations of poly(amidoamine) and poly(propyleneimine) dendrimers /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3025648.
3
He, Min. "Immobilization of poly(amidoamine), PAMAM, dendrimers on zirconia chromatographic support." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0004/MQ59813.pdf.
4
Jones, Nicholas Andrew. "DNA-poly(amidoamine) complexes for gene delivery : a physicochemical description." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299707.
5
Gargiuli, Joseph Fernand. "Synthesis and modification of water-soluble hyperbranched poly(amidoamine)s." Thesis, Durham University, 2002. http://etheses.dur.ac.uk/3871/.
Анотація:
The multi-step syntheses of two water-soluble AB(_2) monomers, N-acryloyl-1,2- diaminoethane hydrochloride and N-acryloyl-1,2-daminoethane, are reported. The melt polymerisation at 210 ºC for 4 hours of N-acryloyl-1,2-diaminoethane hydrochloride gave, by Michael additions of the terminal ammonium salts (B(_2) groups) of a monomer molecule or growing oligomer with the unreacted vinyl double bond (A group) of another monomer molecule or growing oligomer, hyperbranched macromolecules. High degrees of conversion, determined using (^1)H NMR spectroscopy, were obtained and a degree of branching, determined using (^15)N NMR spectroscopy, was found to be equal or close to 1. However, this method proved difficult to reproduce and the alternative aqueous solution polymerisation at 100 ºC for 10 days of this monomer was investigated. The use of ampoules closed with Teflon taps as reactors lead to polymers displaying random signs of free radical polymerisation and high degrees of conversion due to such side-reaction, whereas, the alternative use of sealed Carius tubes lead to lower DP materials displaying no significant signs of free radical side-reactions. The kinetic study of this polymerisation allowed the determination of the rate constant associated with the oligomer growth and the MALDI analysis of these polymers revealed an evolution with time of the oligomer molecular weight distribution with time in agreement with the theoretical prediction. This last study also revealed that at least 70% of the molecules were not cyclised. On the other hand, the aqueous solution polymerisation of the corresponding free base monomer, N-acryloyl-1,2- diaminoethane, at 100 ºC for 90 minutes lead to hyperbranched macromolecules with high DP values. The kinetic study did not allow a precise determination of the rate constant associated with the oligomer growth due to the high reactivity of the free terminal amino groups. The MALDI analysis of these polymer samples showed that the evolution with time of the oligomer molecular weight distribution did not follow the theoretical prediction and that these macromolecules were cyclised.
6
REIS, G. A. LINO DOS. "Microfabrication and characterization of cellon-chip platforms on poly (amidoamine) hydrogels." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/148436.
Анотація:
The control of cell growth, proliferation and differentiation on biomaterials surfaces is of fundamental importance for regenerative medicine, prosthetics, or cell-based assays. The microfabrication of cell-on-chip platforms based on a new family of poly (amidoamine) hydrogels, are promising for in vitro and in vivo applications. Hydrogels present characteristics that mimics biological environments, such as the cross-linked nature of the extracellular matrix, the tissue properties (high water content), and the permeability to oxygen and metabolites. Hydrogels based on poly (amidoamine) results in an optically transparent, biocompatible and fully biodegradable substrate recommended for body implants that are minimally invasive, and naturally eliminated by human body. In my PhD work I intended to use microfabricated hydrogels for fine-tuning the contact guidance of cells. As microfabrication tools I set up reaction injection moulding for producing features down to 100 µm and developed a novel approach relying on electron beam lithography. This innovating microfabrication consists in the ability of directly writing patterns on already cross-linked hydrogels, with the capability of producing structures at sub-micrometric scale. The exposure to the electron beam produces particular modifications enabling the control of physico-chemical properties of irradiated area. I obtained a selective attachment of proteins as a function of the electron-beam dose; an exclusive adhesion and growth of neural cells on the exposed surfaces; and the control of neurite outgrowth guidance along a microfabricated network. These results offer new perspectives to build physiological microenvironments or cell-on-chip platforms, based on a novel class of microfabricated hydrogels.
7
Bitto, Alexandro [Verfasser], and Rolf [Akademischer Betreuer] Mülhaupt. "Cellulose-Nanofüllstoffe und mehrfunktionelle Bio-Amidoamine für thermoplastische Biocompounds und isocyanatfreie Polyurethane." Freiburg : Universität, 2011. http://d-nb.info/112346474X/34.
8
Hill, P. "Biological characterisation of poly(amidoamine)s as DNA carriers for gene therapy." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285644.
9
Richardson, Simon Clifford Wainwright. "Characterisation of poly(amidoamine)s and chitosan as potential intracytoplasmic delivery systems." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369187.
10
Rippey, Julie M. "Spectroscopic investigations of acrylodan dye interactions with poly(amidoamine) and poly(propyleneimine) dendrimers." Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6107.
Анотація:
Thesis (M.S.)--University of Missouri-Columbia, 2008.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed July 13, 2009). Includes bibliographical references.
11
Gevorgyan, S. "NOVEL POLY(AMIDOAMINE) NANOPARTICLES DESIGNED FOR DRUG DELIVERY TO THE CENTRAL NERVOUS SYSTEM." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/366799.
Анотація:
With the aging population, central nervous system diseases are becoming increasingly widespread. However, the treatment of such diseases represents a challenge mainly due to the presence of the blood-brain barrier, which effectively blocks most of drugs to pass into the central nervous system and impedes the treatment of diseases. Therefore, effective ways of drug transport to the central nervous system are highly required.
Polymeric nanoparticles are drug delivery vectors that have high specificity to their targeted sites and increasingly enhance the stability of encapsulated drugs. Poly(amidoamines) are a promising family of synthetic polymers that can be used in nanoparticles synthesis. Nanoparticles synthesized from linear poly(amidoamines) show very good biocompatibility levels and specific targeting properties. Nevertheless, those nanoparticles are mainly synthesized by self-assembly and usually lack long-term stability.
In this study we developed innovative poly(amidoamine) nanoparticles synthesized by ultraviolet light assisted photo-crosslinking. The synthesis method had an advantage of being simple, did not require toxic organic solvents and was shown to be easily scaled-up. Moreover, poly(amidoamine) nanoparticles were coated by Polysorbate 80 surfactant, which not only increased the nanoparticles stability but also gave them central nervous system targeting properties. Poly(amidoamine) nanoparticles were able to successfully encapsulate model therapeutic compounds and release them in a slow and controlled manner. Furthermore, the nanoparticles showed high permeability levels across an in vitro blood brain barrier model.
The developed poly(amidoamine) nanoparticles show great potential to be used as delivery vectors to the central nervous system.
12
Pollock, Neal. "The synthesis, immobilisation and characterisation of poly(amidoamine) dendrons on plasma polymer thin films." Thesis, University of Sheffield, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500151.
13
Franckevičius, Marius. "Excited-state dynamics of PPI and PAMAM dendrimers functionalized with photochromic terminal groups." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2011. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20111003_114600-62082.
Анотація:
Dendrimers are multivalent, well-defined materials that constitute a new class of polymer macromolecules. They have been extensively studied over the past several decades mainly due to their exceptional structure properties. The size of molecule, number of terminal groups, molecular weight and several other properties of dendrimers could be precisely controlled during synthesis.
The main goal of this thesis is to investigate the optical properties and light induced photochemical reaction dynamics within the PPI and PAMAM dendrimers functionalized by CAzPA and ESA type terminal groups by means of several spectroscopic techniques. Because photochromism of CAzPA and ESA type terminal groups is associated with light induced isomerization and tautomerization photochemical reactions, the main attention of present thesis was devoted to investigate dynamical properties of functionalized dendrimers as an influence of dendrimer type and its generation.
Investigations of dynamic properties of PPI and PAMAM dendrimers functionalized with the CAzPA terminal groups have shown that isomerization rate is insensitive to dendrimer type, solvent and excitation wavelength. The isomerization rate of the dendrimer films take place in about 15 ps and it is only seven times slower than in dendrimer solvent.
Both experimental and theoretical optical studies performed on PPI dendrimers functionalized with the ESA type terminal groups reveal four stable tautomeric forms with different energy in the... [to full text]Dendrimerai tai naujai dendritinių polimerų klasei priskiriamos makromolekulės. Jų dydis, funkcinių grupių skaičius yra tiksliai apibrėžti ir gali būti kontroliuojami sintezės metu. Dėl išskirtinių struktūrinių savybių, dendrimerai jau keletą dešimtmečių yra intensyviai tiriamos medžiagos. Pagrindinis disertacijos tikslas yra ištirti PPI ir PAMAM dendrimerų, funkcionalizuotų CAzPA ir ESA fotochrominiais junginiais optines savybes bei šviesa inicijuotų fotocheminių reakcijų dinamiką panaudojus kelias tyrimų metodikas. Kadangi CAzPA ir ESA junginių fotochromizmas yra susijęs su šviesa indukuota izomerizacijos bei tautomerizacijos fotocheminėmis reakcijomis, todėl darbe buvo siekiama ištirti šiais junginiais funkcionalizuotų dendrimerų dinaminių savybių priklausomybę nuo dendrimero tipo bei jo generacijos. Ištyrus PPI ir PAMAM dendrimerų funkcionalizuotų CAzPA junginiais plėvelių ir tirpalų dinamines savybes, buvo nustatyta, kad izomerizacijos sparta nepriklauso nuo dendrimero tipo, tirpiklio ir žadinančios spinduliuotės energijos. Dendrimerų plėvelių sužadintos būsenos relaksacijos trukmė yra apie 15 ps, o tai apie 7 kartus lėčiau nei tirpaluose. Eksperimentiškai ir teoriškai ištyrus skirtingų generacijų PPI dendrimerų funkcionalizuotų ESA fotochrominiais junginiais optines savybes, buvo nustatytos keturios stabilios ESA funkcinių grupių tautomerinės formos, kurių pagrindinės būsenos energijos yra skirtingos. Skirtingų dendrimero generacijų sužadintos būsenos dinamikos... [toliau žr. visą tekstą]
14
Franckevičius, Marius. "Sužadintos būsenos dinamika PPI ir PAMAM dendrimeruose funkcionalizuotuose fotochrominiais junginiais." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2011. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2011~D_20111003_114348-59250.
Анотація:
Dendrimerai tai naujai dendritinių polimerų klasei priskiriamos makromolekulės. Jų dydis, funkcinių grupių skaičius yra tiksliai apibrėžti ir gali būti kontroliuojami sintezės metu. Dėl išskirtinių struktūrinių savybių, dendrimerai jau keletą dešimtmečių yra intensyviai tyrinėjamos medžiagos.
Pagrindinis disertacijos tikslas yra ištirti PPI ir PAMAM dendrimerų, funkcionalizuotų CAzPA ir ESA fotochrominiais junginiais optines savybes bei šviesa inicijuotų fotocheminių reakcijų dinamiką panaudojus kelias tyrimų metodikas. Kadangi CAzPA ir ESA junginių fotochromizmas yra susijęs su šviesa indukuota izomerizacijos bei tautomerizacijos fotocheminėmis reakcijomis, todėl darbe buvo siekiama ištirti šiais junginiais funkcionalizuotų dendrimerų dinaminių savybių priklausomybę nuo dendrimero tipo bei jo generacijos.
Ištyrus PPI ir PAMAM dendrimerų funkcionalizuotų CAzPA junginiais plėvelių ir tirpalų dinamines savybes, buvo nustatyta, kad izomerizacijos sparta nepriklauso nuo dendrimero tipo, tirpiklio ir žadinančios spinduliuotės energijos. Dendrimerų plėvelių sužadintos būsenos relaksacijos trukmė yra apie 15 ps, o tai apie 7 kartus lėčiau nei tirpaluose.
Eksperimentiškai ir teoriškai ištyrus skirtingų generacijų PPI dendrimerų funkcionalizuotų ESA fotochrominiais junginiais optines savybes, buvo nustatytos keturios stabilios ESA funkcinių grupių tautomerinės formos, kurių pagrindinės būsenos energijos yra skirtingos. Skirtingų dendrimero generacijų sužadintos būsenos dinamikos... [toliau žr. visą tekstą]Dendrimers are multivalent, well-defined materials that constitute a new class of polymer macromolecules. They have been extensively studied over the past several decades mainly due to their exceptional structure properties. The size of molecule, number of terminal groups, molecular weight and several other properties of dendrimers could be precisely controlled during synthesis. The main goal of this thesis is to investigate the optical properties and light induced photochemical reaction dynamics within the PPI and PAMAM dendrimers functionalized by CAzPA and ESA type terminal groups by means of several spectroscopic techniques. Because photochromism of CAzPA and ESA type terminal groups is associated with light induced isomerization and tautomerization photochemical reactions, the main attention of present thesis was devoted to investigate dynamical properties of functionalized dendrimers as an influence of dendrimer type and its generation. Investigations of dynamic properties of PPI and PAMAM dendrimers functionalized with the CAzPA terminal groups have shown that isomerization rate is insensitive to dendrimer type, solvent and excitation wavelength. The isomerization rate of the dendrimer films take place in about 15 ps and it is only seven times slower than in dendrimer solvent. Both experimental and theoretical optical studies performed on PPI dendrimers functionalized with the ESA type terminal groups reveal four stable tautomeric forms with different energy in the... [to full text]
15
Hartmann, Laura. "Synthese monodisperser, multifunktionaler Poly(amidoamine) und ihre Anwendung als nicht-virale Vektoren für die Gentherapie." Phd thesis, Universität Potsdam, 2007. http://opus.kobv.de/ubp/volltexte/2007/1312/.
Анотація:
Die vorliegende Arbeit beschäftigt sich mit der Synthese monodisperser, multifunktionaler Poly(amidoamine) (PAAs). Die Klasse der PAAs ist besonders interessant für eine Anwendung im Bereich der Biomedizin, da sie meist nicht toxisch ist, eine sehr geringe Immunogenizität zeigt und eine erhöhte Zellmembranpermeabilität besitzt. Allerdings ist der Einsatz linearer PAAs bisher limitiert, da ihre Synthese nur den Zugang von hoch-polydispersen Systemen mit einer streng alternierenden oder statistischen Verteilung von Funktionalitäten erlaubt. Es ist daher von großem Interesse diese Polymerklasse durch die Möglichkeit eines sequenzdefinierten Aufbaus und der Integration von neuen Funktionalitäten zu verbessern.
Um dies zu ermöglichen, wurden, vergleichbar mit der etablierten Festphasensynthese von Peptiden, schrittweise funktionale Disäure- und Diamin-Bausteine an ein polymeres Träger-Harz addiert. Der sequenzielle Aufbau ermöglicht die Synthese monodisperser PAAs und die Kontrolle über die Monomersequenz. Die Wahl der Monomer-Bausteine und ihrer Funktionalitäten kann dabei für jede Addition neu getroffen werden und entscheidet so über die Sequenz der Funktionalitäten im Polymerrückgrat.
Die verwendete Chemie entspricht dabei der Standardpeptidchemie, so dass mit Hilfe eines Peptidsynthese-Automaten die Synthese vollständig automatisiert werden konnte. Die Verwendung spezieller Trägerharze, die bereits mit einem synthetischen Polymerblock wie PEO oder auch mit einem Peptid vorbeladen waren, erlaubt die direkte Synthese von PEO- und Peptid-PAA Blockcopolymeren.
Da die hier dargestellten PAAs später auf ihre Eignung als multivalente Polykationen in der Gentherapie getestet werden sollten, wurden zunächst Bausteine gewählt, die den Einbau verschiedener Aminfunktionalitäten ermöglichen. Die Bausteine müssen dabei so gewählt sein, dass sie kompatibel sind mit der Chemie des Peptidsynthesizers und eine quantitative Addition ohne Neben- oder Abbruchreaktionen garantieren. Darüber hinaus ist der Einbau von Peptidsequenzen und Disulfid-Einheiten in die PAA-Kette möglich, die z. B. für einen selektiven Abbau des Polymers im Organismus genutzt werden können.
Zusammenfassend lässt sich feststellen, dass die in dieser Arbeit vorgestellten PAA-Systeme großes Potenzial als nicht-virale Vektoren für die Gentransfektion bieten. Sie sind nicht toxisch und zeigen Zellaufnahme-Effizienzen von bis zu 77%. Die Gentransfereffizienz ist im Vergleich zu etablierten Polymer-Vektoren zwar noch sehr gering, aber die bisherigen Versuche zeigen bereits eine mögliche Ursache, nämlich die schlechte Freisetzung des Genmaterials innerhalb der Zelle. Eine Lösung dieses Problems bietet jedoch die weitere Modifizierung der PAA-Systeme durch den Einbau von Sollbruchstellen. Diese Sollbruchstellen ermöglichen einen programmierten Abbau des Polymers innerhalb der Zelle und damit sollte die Freisetzung des Genmaterials vom Träger deutlich erleichtert werden. Mögliche Bruchstellen sind z. B. enzymatisch gezielt spaltbare Peptideinheiten oder Disulfid-Einheiten, wie sie bereits als Bausteine für die PAA-Synthese vorgestellt wurden (vergl. Kapitel 4.4). Da nur innerhalb der Zelle ein reduzierendes elektrochemisches Potential besteht, werden z. B. Disulfid-Einheiten auch nur dort gespalten und bieten außerhalb der Zelle ausreichende Stabilität zum Erhalt der Polyplexstruktur.
Neben einer Anwendung in der Gentherapie bieten die hier vorgestellten PAA-Systeme den Vorteil einer systematischen Untersuchung von Struktur-Eigenschafts-Beziehungen der Polyplexe. Es wurden verschiedene Zusammenhänge zwischen der chemischen Struktur der PAA-Segmente und der Art und Stärke der DNS-Komprimierung aufgezeigt. Die Komprimierungsstärke wiederum zeigte deutlichen Einfluss auf die Internalisierungsrate und damit auch Transfektionseffizienz. Darüber hinaus zeigte sich ein drastischer Einfluss des PEO-Blocks auf die Stabilisierung der Polyplexe sowie deren intrazelluläre Freisetzung bei Zusatz von Chloroquin.
Dennoch bleiben aufgrund der Komplexität der Zusammenhänge noch viele Mechanismen der Transfektion unverstanden, und es muss Aufgabe folgender Arbeiten sein, das Potential der hier eingeführten monodispersen PAA-Systeme weiter auszuloten. So wäre z. B. eine Korrelation der Kettenlänge mit den Parametern der Polyplexbildung, der Zellaufnahme und Transfektionseffizienz von großem Interesse. Darüber hinaus bietet der Einbau von Sollbruchstellen wie kurzen Peptidsequenzen oder den hier bereits eingeführten Disulfid-Einheiten neue Möglichkeiten der gezielten Freisetzung und des programmierten Abbaus, die näher untersucht werden müssen.
Neben der Anwendung im Bereich der Gentransfektion sind außerdem andere Gebiete für den Einsatz von monodispersen multifunktionalen PAAs denkbar, da diese kontrollierbare und einstellbare Wechselwirkungen ermöglichen.Recently, linear poly(amidoamine)s (PAAs) have received considerable attention due to their excellent biocompatibility and ease of synthesis.[1] PAAs are multifunctional polymers, which often exhibit low inherent immunogenicity and reduced cyto- as well as hemotoxicity in contrast to established, cationic polymers such as poly(ethylene imines) (PEI) or poly(L-lysines) (PLL).[2] This makes PAAs highly suitable for biomedical and pharmacological applications in the fields of drug and gene delivery.[1,2] However, the full potential of these polymers cannot be accessed since the synthesis proceeds via an uncontrolled polyaddition reaction leading to ill-defined products with Mw/Mn ≥ 2. This does not only make rational design of polymer properties and the precise positioning of functionalities along the polymer backbone difficult, furthermore product registration becomes complicated because legislation requires increasingly more defined products. Here we present a novel synthesis route towards multifunctional, sequence-defined polyamides.[3] A fully automated, solid-phase polymer synthesis was developed and utilized to obtain linear PAA segments. These exhibit no molecular weight or chemical distributions due to their monodispersity (Mw/Mn = 1) and their controlled monomer sequence. The compatibility of the PAA-synthesis with the standard Fmoc/tBu solid-phase supported peptide synthesis has been preserved, making this route a versatile approach to peptide-PAA (Pep-PAA) and poly(ethylene oxide)-PAA (PEO-PAA) conjugates. Several Pep-PAA and PEO-PAA conjugates were synthesized, exhibiting PAA segments with different cationic functionalities. These conjugates were analyzed concerning their cytotoxicity showing very promising results. Additionally their potential to complex plasmid-DNA and to form so-called polyplexes for non-viral gene delivery was tested. A strong relationship between the monomer sequence and the polyplex structure was observed, depending on the balance and total amount of tertiary, secondary and primary amine functionalities within the PAA-segment. Moreover the monomer sequence has a strong influence on the biological properties such as the cell-internalization of polyplexes as well as the transfection activity. This clear correlation between the chemical assembly and the resulting biological properties may help to further the understanding of the mechanisms of gene delivery by polymeric carriers and hence to promote the rational design of better suited systems. Even if the transfection activity for the PAA-polpylexes might still be not comparable to the established “gold standard” PEI, their low level of toxicity and the possibility to improve the system by adjusting the monomer sequence shows great potential as carrier systems in drug or gene delivery.
16
Hlavinka, Mark Louis. "Dizinc organometallics based on pre-organized binucleating bis(amidoamine) ligands; synthesis, structure, and reactivity of zinc enolates." Diss., Connect to online resource, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3207756.
17
Silva, Klaydison. "New approach to hematite recovery from ultrafine iron ore processing tailings : From fundamental studies to on-site pilot testing." Electronic Thesis or Diss., Université de Lorraine, 2022. http://www.theses.fr/2022LORR0287.
Анотація:
L'objectif principal du travail de thèse est de définir et d'expliquer le comportement différentiel de l'hématite et des silicates à l'aide de réactifs plus sélectifs dans la flottation inverse des schlammes de minerai de fer. La méthodologie proposée est basée sur l'utilisation des effets des réactifs de flottation pour augmenter la récupération des particules fines des résidus de traitement du minerai de fer. Des méthodes spectroscopiques et électrocinétiques permettront de comprendre la différence d'hydratation de la surface minérale. Des essais de flottation à l'échelle du laboratoire et une modélisation moléculaire du mécanisme d'interaction entre les collecteurs et la surface de quartz et d'hématite seront également réalisés. Des essais pilotes valideront les résultats obtenus dans ce travail de thèse multi-échelleThe main objective of the thesis work is to define and explain the differential behavior of hematite and silicates using more selective reagents in the reverse flotation of iron ore slimes. The proposed methodology is based on using the effects of flotation reagents to increase the recovery of fine particles from iron ore processing tailings. Spectroscopic and electrokinetic methods will make it possible to understand the difference in hydration of the mineral surface. Laboratory-scale flotation tests and molecular modeling of the mechanism of interaction between the collectors and the surface of quartz and hematite will also be carried out. Pilot tests will validate the results obtained in this multi-scale thesis work
18
Anthiya, Ramamoorthi Shubaash. "Development of miRNA-mimic nanoparticles for the treatment of brain tumours." Thesis, Angers, 2016. http://www.theses.fr/2016ANGE0052/document.
Анотація:
Les glioblastomes sont des tumeurs cérébrales très agressives présentant une médiane de survie de 15 mois malgré l’usage du traitement de référence. Parmi les stratégies innovantes anti-glioblastome, les microARNs (miARN) constituent de nouvelles cibles et des outils thérapeutiques à fort potentiel. En outre, pour atteindre les cellules tumorales notamment au niveau loco-régional, les miARNs nécessitent d’être administrés grâce à des vecteurs sûrs et efficaces. L’objectif de ce travail a été de développer un système nanoparticulaire original de polyamidoamine réticulé (PAA) capable de véhiculer des miARNs au niveau cellulaire et tissulaire. Dans un premier temps, un test basé sur l’expression de la luciférase a été mis au point afin d’étudier la cytotoxicité et l’efficacité de nanoparticules des miARNs. Dans un second temps,des nanoparticules PAA-miARN ont été développées. Différentes conditions de formulation ont été testées afin d’optimiser la complexation entre miARNs et polymères. En l’absence d’efficacité cellulaire significative des premiers objets obtenus, des modifications du procédé de formulation ont été apportées, permettant une plus grande stabilité et une meilleure efficacité. Une fonctionnalisation par greffage de groupements biotine à des complexes PAA thio-réticulés a amélioré l’efficacité des internalisations. En conclusion, ce travail a permis le développement d’une méthode simple et rapide pour l’évaluation de l’efficacité et de la cytotoxicité de nanoparticules de miARN. La stabilité des nanoparticules a été augmentée par réticulation de thiolet leur internalisation a été améliorée par le greffage,adapté et modulable, d’un ligand cellulaireGlioblastoma are aggressive brain tumours with a median survival of 15 months even with the best currently available treatment options. microRNAs (miRNA) are ~23 nucleotide natural silencing RNAs that have great potentials to improve cancer treatment outcomes. Lack of a safe, stable and efficient delivery system has, however, hindered the use of miRNAs inclinical applications. The aim is therefore to develop amiRNA delivery system adapted to glioblastoma using linear chain cationic polyamidoamine (PAA) polymers.The first part involved the development of luciferase assay that combined the measurement of gene-knockdown efficiency and cytotoxicity of miRNA nanoparticles. The simple two-step procedure was more effective and sensitive compared to the conventional protein-based normalization method. The second part was focused on the development of miRNA nanoparticles. In the initial phase, conditions required for maximum miRNA-polymer binding was achieved, however, the newly developed miRNA-PAA nanoparticlesdid not produce significant functional gene-knockdown after cell treatment. The second stage was focused on the optimization of nanoparticle formulation as a function of stability in physiologicalionic concentration. Stable PAA-nanoparticles displaying moderate cellular uptake and gene-knockdown were obtained. The final stage of development was focused on PAA-nanoparticle tagging with biotin, which improved their cellular uptake. This work developed simple and informative luciferase assay ; the stability of miRNA-PAA-nanoparticles was improved by thiol-crosslinking and the functional performance was strongly enhanced by a simple butsmart method of ligand tagging
19
Morosini, Vincent. "Pour une amélioration de la thérapie photodynamique appliquée à la cancérologie : Potentialités des dendrimères poly(amidoamine) et des Quantum Dots CdTe adressés par l'acide folique." Phd thesis, Université Henri Poincaré - Nancy I, 2010. http://tel.archives-ouvertes.fr/tel-00547015.
Анотація:
L'efficacité de la thérapie photodynamique (PDT) est confrontée à plusieurs verrous : les photosensibilisateurs (PSs) utilisés en clinique ne sont pas adaptés à la fenêtre thérapeutique, ils subissent un photoblanchiment lors du traitement, et leur nature organique pose des problèmes de solubilité en milieu biologique. Ils présentent également une faible sélectivité envers les tissus tumoraux à traiter. Dans le cadre de cette thèse, trois approches visant une amélioration de la PDT appliquée à la cancérologie ont été développées : la vectorisation, l'adressage, et l'optimisation de nouveaux PSs. La synthèse de structure PS/vecteur a permis d'élaborer des structures hydrophiles capables de vectoriser des PSs hydrophobes. Des porphyrines ont ainsi été greffées sur des dendrimères polyamidoamine (PAMAM) dissymétriques. La conservation des propriétés photophysiques des PSs après leur couplage au dendrimère a été mise en évidence. Des quantum dots (QDs), grâce à la modularité de leurs propriétés photophysiques et leur capacité à résister au photoblanchiment, ont été synthétisés et utilisés comme nouvelle classe d'agents photosensibilisants. Ces QDs ont été préparés afin d'être hydrophiles et utilisables dans la fenêtre thérapeutique de la PDT. Une étude in vitro des QDs couplés à l'acide folique a mis en évidence leur activité photodynamique. Des études réalisées par une approche de plans d'expérience a permis de hiérarchiser les facteurs expérimentaux en fonction de leurs impacts sur l'activité photodynamique. Nous avons en particulier montré une amélioration de la sélectivité des conjugués envers les cellules surexprimant le récepteur à l'acide folique.
20
Xu, Yinhui Zhao Dongye. "Removal of copper(II) and lead(II) from soils by poly(amidoamine) dendrimers and reductive immobilization of chromium(VI) by stabilized zero-valent iron nanoparticles." Auburn, Ala., 2006. http://repo.lib.auburn.edu/Send%208-7-07/XU_YINHUI_21.pdf.
21
Ferrari, E. "POLYMERIC MATERIALS FOR THE QUANTITATIVE AND REVERSIBLE ABSORPTION OF ORGANIC AND INORGANIC WATER CONTAMINANTS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/229550.
Анотація:
Water pollution is one of the most serious environmental problems the world faces today. Due to a progressive change in environmental perception in developed countries, great attention is currently given to specific pollutants, both of natural and human origin, often labeled as organic and inorganic micropollutants. Micropollutants can have severe implications both on ecology and human health even in very low concentration in water, being potentially toxic and carcinogenic, and are included in the EU PP (Priority Pollutants) list. The current water purification treatments are affected by many limitations and do not significantly lower the concentration of micropollutants, unless the treatment is carried out, if technically possible, to such an extent to become not economically sustainable. In this context, the aim of this PhD thesis is the development and characterization of polymeric absorbing materials for the quantitative and reversible removal of organic and inorganic micro-pollutants from water. These materials are based on poly(amidoamine)s (PAAs), cyclodextrins and renewable resources such as guar gum and hemicelluloses. The synthetic procedures adopted are simple, eco-friendly and employ water as solvent. The materials proved able to absorb either inorganic (Cu(II), Co(II), Cd(II), Pb(II), Mn(II), Zn(II), Fe(II), Ni(II), Cr(VI)) or organic micropollutants (chloroform, halothane, tetrachloroethylene, o-toluidine) and were competitive with other sorbents reported in literature. They could also be regenerated and recycled without loss of absorption performance.
22
Fenili, F. "NOVEL BIOACTIVE AND BIODEGRADABLE BIOMATERIALS OF POLY(AMIDOMINE) STRUCTURE." Doctoral thesis, Università degli Studi di Milano, 2010. http://hdl.handle.net/2434/150128.
Анотація:
PhD thesis of Fabio Fenili R07830
Tutor: Prof. Elisabetta Ranucci
Coordinator: Prof. Dominique Roberto
NOVEL BIOACTIVE AND BIODEGRADABLE BIOMATERIALS OF POLY(AMIDOAMINE)S STRUCTURE
Biomaterials are any materials designed to interface with biological system to evaluate, support or replace any tissue, organ or body function. Metals, ceramics, polymers and composites are biomaterials commonly used every day for biomedical applications in the form of sutures, vascular grafts, heart valves, intraocular lenses, dental and orthopaedic implants, pacemakers, biosensors, drug delivery systems, gene carriers, etc.
Compared to the other types of biomaterials, polymeric biomaterials offer the advantages that can be prepared in different compositions with a variety of structures and properties. In particular, in the case of biodegradable polymers, their physical, chemical, and biological characteristics as well as degradation rate can be tuned to meet specific applications.
Among polymeric biomaterials, poly(amidoamine)s (PAA), a family of biodegradable and biocompatible polymers, can be considered as promising materials for different pharmaceuticals and biotechnological applications.
The present PhD project aimed at the design of novel poly(amidoamine)s biomaterials of different architecture for diversified biomedical applications, each representing a distinct research sub-objective.
Poly(amidoamine)-gelonin conjugates as potential anti-cancer drugs.
Two PAAs bearing pendant 2-ethenyldithiopyridine (ISA1-SSPy and ISA23-SSPy) were used to investigate their ability to mediate intracellular delivery of the type I ribosome-inactivating gelonin. The strategy adopted consists of a three step synthesis. In the first step, a cystamine crosslinked PAA was synthesised generating a hydrophilic tri-dimensional network. In the second step, the hydrogel obtained was de-reticulated by direct disulfide exchange reaction with dipyridyl disulfide. Finally, the linear and soluble PAA-SSPy thus obtained was conjugated via thiol-disulfide exchange reaction to a thiol-containing gelonin, a ribosom inactivating protein. Two different recombinant protein, encoding gelonin with an N-terminal 6xHistidine (H or His) and V5 epitope tag (6H-V5 Gelonin) and gelonin encorporating a C-terminal HA and 6xHis tag flanking a cysteine residue (Gelonin HA-Cys-6H) were prepared introducing the required tag on a gelonin plasmid by polymerase chain reaction (PCR), isolated and purified from E. Coli.
In vitro experiments were performed on B16F10 cells using non-toxic concentration of gelonin and polymeric samples up to 2 mg/ml. ISA1-SSPy promoted the intracytoplasmic delivery of gelonin more efficiently than the parent non-functionalized ISA1 with IC50 values of 100 µg/ml.
The results obtained for ISA1-SSPy-HA-Cys-6H, designed to have a covalent bound between the polymeric vector and the toxin, and ISA1-SSPy-6H-V5 Gelonin were the same, suggesting a non specific conjugation to the thiol-groups in the Gelonin HA-Cys-6H.
This findings could be attributed both to the ability of ISA1-SSPy to react with protein’s disulfide groups and to the interactions between the ethenyl-dithiopyridine pendants and the hydrophobic domains of the protein, giving stable complexes. ISA23-SSPy was unable to mediate toxin delivery.
Tricarbonyl-rhenium complexes of a thiol-functionalized amphoteric poly(amidoamine).
In this work we investigate the possibility to design new polymeric radiopharmaceuticals using poly(amidoamine)s polymers (PAA)s and [Re(CO)3(H2O)3]+. An amphoteric thiol-functionalized ISA23 copolymer (ISA23SH10%) has been obtained following a two step pathway: the first was the synthesis of polymers containing cystamine-m-Boc pendants, the second one was the reduction of the disulphide bond in the presence of dithiotreitol (DTT) as reducing agent. The copolymer was able to tightly bind up to 0.8 equivalents of Re(CO)3+ fragments, with respect to the thiol groups. The polymeric complexes, containing 0.5 or 0.8 equivalents of rhenium, respectively, were easily obtained by reacting ISA23SH10% with [Re(CO)3(H2O)3](CF3SO3), in aqueous solution, at pH 5.5. The complexes maintained the water solubility of the parent polymer and were stable in physiological conditions and also in the presence of cysteine. The coordination of the Re(CO)3 fragment involves the cysteamine-deriving moiety.
A detailed 1H, 13C and 15N NMR characterization of ISA23SH10% and of complex with 0.8 equivalents of Re(CO)3+ provided a clear evidence that the binding of rhenium occurs by chelation through the S and N atoms of the -amino-thiolate fragment. A morphological evaluation by TEM analysis showed that both complexes form nanoparticles with a regular spherical morphology and a narrow size distribution. In vivo toxicological tests showed that ISA23SH10% is highly biocompatible, with a maximum tolerated dose of 500 mg/kg. Preliminary biological studies in vitro and in vivo have been performed also on both complexes. No hemolytic activity was observed, up to a concentration of 5 mg/mL, neither citotoxicity effect was observed on Hela cell after 48 h of incubation. No toxic side effects were observed after the intravenous injection in mice of the two complexes in doses up to 20 mg/kg.
Poly(amidoamine)-based hydrogels as scaffold for tissue engineering applications.
In this work a new synthetic method has been developed leading to PAA hydrogels with improved mechanical strength and good biological properties for tissue engineering applications. In particular a two-step pathway has been followed: in the first step an acryloyl end-capped linear Agma1 oligomer was synthesised using a controlled excess of the bisacrylamide; in the second step the oligomer was photopolymerized by UV irradiation producing hydrogels with the required mechanical characteristics.
Using this new synthetic procedure, PAA-UV made hydrogels with different form and shape were prepared. In particular, tubular scaffolds with 1 mm inner diameter were tested in vivo as conduit for nerve regeneration in a rat sciatic nerve cut model. The implants were analyzed at 30, 90 and 180 days post-surgery and resulted particularly promising in many important respects, such as biodegradability, biocompatibility, lack of inflammatory reaction upon degradation and capability of promoting optimum morphological and functional nerve regeneration. The regenerated nerves showed several interesting signs of morphological improvements even at 30 days post-surgery. At 180 days the scaffold was almost completely reabsorbed and the regenerated nerve morphologically comparable to the control animals.
Cationic PAA as non-viral vector for gene therapy.
Recently, a new linear and amphoteric but prevailing cationic PAA, nicknamed Agma1 (Scheme 4) has been successfully tested as trasfection promoters in vitro without any signs of toxicity is despite its polycationic behavior. Based on this premise, in this work, three samples of Agma1 having different molecular weights, named AGMA5 ( =5100), AGMA10 ( =10100) and AGMA20 ( =20500) were tested as nucleic acid carriers in order to establish the relationship between the molecular weight of the samples and their gene transfer ability. All samples proved able to complex DNA forming stable nanoparticles with positively charged surface and dimensions depending on the weight/weight ratio between polymer and DNA, and pH. The molecular weight of the polymeric samples had a significant influence on their efficiency as DNA carrier. AGMA10 and AGMA20 showed good transfection ability compared to AGMA5 which was almost ineffective even at a 1:100 w/w DNA/polymer ratio. The polyplex nanoparticles proved highly biocompatible and were easily internalized in cells escaping from the endosomal vesicles and mostly localizing in perinuclear region. AGMA10 was chosen for animal experiments and proved effective also in vivo. A 1:30 DNA/AGMA10 polyplex after intravenous administration to mice induced remarkable gene expression in the liver but not in other organs, including lungs without detectable toxic side effects.
23
Dietrich, Sascha. "(Metallo-)Dendrimers in Catalysis, Nanoparticle Stabilization and Biological Application." Doctoral thesis, Universitätsbibliothek Chemnitz, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-82016.
Анотація:
(Metallo-)Dendrimers in Catalysis, Nanoparticle Stabilization
and Biological Application
Technische Universität Chemnitz, Fakultät für Naturwissenschaften
Dissertation 2011, 165 Seiten
Die vorliegende Dissertationsschrift befasst sich mit der Darstellung, Charakterisierung und Anwendung neuartiger (Metallo-)Dendrimere. Den Schwerpunkt der Arbeit bildet dabei die terminale Funktionalisierung (Poly)amidoamin-basierender Dendrimere kleiner Generationen.
Durch Standardpeptid-Knüpfungsreaktionen von 1,1´-(Diphenylphosphino)ferrocen-carbonsäure an dendritische (Poly)amidoamine ist eine Serie entsprechend funktionalisierter Metallodendrimere zugänglich. Die metallorganischen, Dendrimer-immobilisierten Engruppen können durch Zugabe von [Pd(3-C3H5)Cl]2 in heterobimetallische Übergangsmetallkomplexe umgewandelt werden und finden Einsatz als katalytisch aktive Systeme in C,C-Kreuzkupplungsreaktionen nach Heck.
Ein weiterer Gegenstand der Arbeit ist die terminale Modifikation von (dendritischen) Ami-nen mit (Sp)-2-(Diphenylphosphino)ferrocen-1-carbonsäure. Nach erfolgter Umsetzung mit [Pd(3-C3H5)Cl]2 werden die erhaltenen planar-chiralen Verbindungen als Katalysatoren in asymmetrischen allylischen Substitutionsreaktionen eingesetzt.
Ferner ist die Darstellung (Oligo)ethylenglykolether-terminierter (Poly)amidoamin-Dendrimere beschrieben. Diese werden als Stabilisatoren zur in-situ Generierung von Gold- sowie Magnetit-Nanopartikeln eingesetzt. Der Einfluss der dendritischen Template auf die Kolloidgrößen und Morphologien sowie die Eigenschaften der gebildeten Hybridmaterialien werden aufgezeigt.
Darüber hinaus befasst sich die Arbeit mit der Verwendung biokompatibler (Oligo)ethylenglykolether-Dendrimere als Wirkstoffträger für Zytostatika bei der Krebsthera-pie. Die im Rahmen von in vitro Untersuchungen erhaltenen Ergebnisse werden präsentiert.
24
Heldt, Jan-Martin. "Apport des dendrimères organométalliques à la mise au point d' un nouveau format d' immunodosage CMIA en phase solide." Paris 6, 2005. http://www.theses.fr/2005PA066412.
25
Rossi, E. "AN ALTERNATIVE STRATEGY FOR ADIPOSE TISSUE RECONSTRUCTION." Doctoral thesis, Università degli Studi di Milano, 2017. http://hdl.handle.net/2434/466585.
Анотація:
Despite clinical treatments for adipose tissue defects, in particular breast tissue reconstruction, have certain grades of efficacy, many drawbacks are still affecting the long-term survival of new formed fat tissue. To overcome this problem, in the last decades, several scaffolding materials have been investigated in the field of adipose tissue engineering. However, a strategy able to recapitulate a suitable environment for adipose tissue reconstruction and maintenance is still missing.
Synthetic polymers gather a series of advantages because they can be chemically modified obtaining hydrogels with desired biochemical, mechanical and degradation properties. Among the synthetic class of polymer, poly(amidoamine)s (PAAs) based hydrogels, containing the 2,2-bisacrylamidoacetic acid-agmatine monomeric unit, are known to have promising biological properties because they can enhance cellular adhesion by interacting with the arginine-glycine-aspartate (RGD)-binding motif of integrins. In this thesis, we first exploited the potential of RGD-mimetic PAA based hydrogels for the establishment of three dimensional (3D) cell culture systems with tunable mechanical and degradation properties. We presented two different approaches for the fabrication of PAA based hydrogels. In the first approach, we copolymerized the PAA oligomers (OPAA) with poly(ethylene glycol) (PEG) to fabricate hydrogels with improved biological, mechanical and optical transparency properties. In the second approach, a synthetic polymeric precursor for cell encapsulation was realized with the aim to combine, by grafting, the adhesive properties of PAAs with the good mechanical integrity of poly(2-hydrox-yethyl)methacrylate (PHEMA) based hydrogels. We demonstrated that with our approaches it is possible to tune the mechanical properties of our hydrogels keeping the adhesive properties typical of pure PAA and providing a tunable platform for 3D cell culture.
Once evaluated the PAA potential to support 3D cell culture, we adopted a biologically and mechanically driven design to fabricate OPAAs macroporous foam (OPAAF) for adipose tissue reconstruction. The scaffold was designed to fulfil three fundamental criteria: capability to induce cell adhesion and proliferation, support of in vivo vascularization and match of native tissue mechanical properties. OPAAs were formed into soft scaffolds with hierarchical porosity through a combined free radical polymerization and foaming reaction. OPAAF is characterized by a high water uptake capacity, progressive degradation kinetics and ideal mechanical properties for adipose tissue reconstruction. Furthermore, OPAAF supported cell adhesion, proliferation and adipogenesis in vitro together with adipose tissue and vessels infiltration in vivo.
ECM is known to be the ideal scaffold for tissue engineering application. In the detail, decellularized adipose tissue proved to have an adipoinuctive effect on adipose stromal cells. Therefore we decided to further implement the biological properties of the OPAAF by decoration with a devitalized adipose tissue matrix.
We first optimized a protocol for the 3D adipogenic differentiation of human primary cells in vitro using a perfusion bioreactor system. The OPAAF efficiently supported human adipose stromal cells (hASCs) differentiation into mature adipocytes. We then decorated the OPAAF with engineered devitalized adipose tissue matrix deposited by hASCs. Two different protocols have been adopted for the decoration, in order to investigate the role of a differentiated and stromal matrix in adipogenic induction. With our approach we efficiently generated hybrid scaffolds combining the positive features of both synthetic and natural biomaterials. The obtained hybrid constructs showed to have an adipoinductive effect on hASCs in absence of any growth factor in vitro and promoted adipogenesis in vivo.
Overall, these results proved that our approach can provide an alternative strategy for adipose tissue reconstruction based on the use of patients cells for the generation of custom made hybrid scaffolds. The engineered adipose tissue could also serve as a 3D model of fat tissue at different stages of differentiation with potential use in drug testing.
26
Alonci, Giuseppe. "Injectable hydrogels for innovative clinical applications." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAF064.
Анотація:
Cette thèse porte sur la conception d'hydrogels injectables pouvant être utilisés en chirurgie mini-invasive, par exemple en dissection endoscopique sous-muqueuse (ESD) ou en réparation de hernie.Les polyamidoamines (PAAm) constituent une classe d'hydrogel intéressante à ces fins. Après avoir étudié les différents facteurs qui affectent leurs propriétés, nous montrons qu'il est également possible d'obtenir des microgels à base de PAAm pour la délivrance de médicaments ou l'encapsulation de cellules. Il est possible de synthétiser des PAAm dégradables qui peuvent être injectés dans la sous-muqueuse de l'estomac pour la ESD.Nous avons montré que les hydrogels hybrides alginate / PAAm peuvent être utilisés pour le traitement percutané de la hernie inguinale directe et des crèmes à base d'hydrogel ont été préparées pour être utilisées pour le colmatage des fistules. Le dernier chapitre de la thèse est consacré à la réticulation de l'acide hyaluronique pour la chirurgie esthétiqueThis thesis deals with the design of injectable hydrogels that can be used in minimally invasive surgery, such as endoscopic submucosal dissection (ESD), percutaneous hernia repair or fistulas closure.Polyamidoamines (PAAm) constitute a class of hydrogel of special interest for these purposes. After studying the different factors that affect their properties, we show that it is also possible to obtain PAAM-based microgels for applications in drug delivery or cell encapsulation.It is possible to synthesize redox-responsive nanocomposite degradable PAAm that can be injected into the submucosa of the stomach to facilitate the ESD.We show that hybrid alginate/PAAm hydrogels can be used for the percutaneous treatment of direct inguinal hernia and hydrogel-based creams have been prepared for use in fistulas closure. The last chapter of the thesis is devoted to the development of a new crosslinking strategy for hyaluronic acid in cosmetic surgery
27
Paes, Lorena Cristine. "Síntese e desenvolvimento de métodos analíticos para o estudo de pró-fármacos dendriméricos potencialmente ativos em doenças negligenciadas." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-14122016-152906/.
Анотація:
Doenças infecciosas parasitárias consideradas negligenciadas representam um grande problema de saúde pública em muitos países e regiões. Os fármacos disponíveis na terapêutica são, em geral, tóxicos e de eficácia discutível. Portanto, a descoberta e o planejamento de novos quimioterápicos são extremamente necessários. Neste contexto, os pró-fármacos dendriméricos podem ser úteis. Porém, é necessário esforço adicional para viabilizar os custos, simplificar as estratégias de síntese e investigar os comportamentos de liberação. Ademais, é importante a melhoria dos métodos analíticos, dos métodos de purificação e identificação dos produtos de síntese, para a determinação das propriedades físico-químicas e atividade biológica, visando à efetiva aplicação desta tecnologia. Face ao exposto, o objetivo deste trabalho foi estudar a identidade, pureza e liberação de dois potenciais pró-fármacos dendriméricos, baseados em 3- hidroxiflavona, planejados para serem ativos em doença de Chagas e leishmaniose. O primeiro, estruturalmente, contendo inositol como núcleo e ramos constituídos por éster da 3- hidroxiflavona com ácido málico e o segundo, estruturalmente contendo o dendrímero PAMAM-G0 (poliamidoamina de geração inicial) como transportador e ácido succínico como espaçante. Desenvolveram-se métodos adequados à determinação da 3-hidroxiflavona por HPLC-UV (Cromatografia líquida de alto desempenho, com detecção no ultravioleta) e MEKC (Cromatografia eletrocinética micelar). Comparando-se esses métodos, o método por HPLC foi mais sensível, preciso e exato na quantificação da 3-hidroflavona, enquanto o método por eletroforese capilar foi mais rápido e de menor custo. O éster da 3-hidroxiflavona com o ácido málico mostrou-se instável em soluções orgânicas, aquosas em diferentes pH e nas condições reacionais de diversas estratégias de síntese avaliadas, o que impediu a obtenção do dendrímero baseado em inositol como núcleo conforme proposto. Já o dendrímero PAMAM-G0 funcionalizado com 3-hidroxiflavona foi sintetizado, purificado e caracterizado com sucesso. Não se observou liberação da 3-hidroxiflavona a partir desse dendrímero em solução gástrica simulada (pH 1,2) e a mesma foi lenta em soluções tampão com pH entre 5,0 e 8,5, a 37,0 ºC. Ensaios de atividade biológica do PAMAM-G0-SUC-3-OH-FLAV em amastigotas de Trypanosoma cruzi, cepas Y(Curitiba) e Y(SS), comparativamente ao benznidazol e ao nifurtimox, mostraram atividade moderada e baixa seletividade.Infectious parasitoses considered neglected diseases represent a great health problem for many countries and areas. Drugs available in the therapeutics are, generally, toxics and do not have good efficacy. So, the discovery and design of new chemotherapeutic agents are extremely needed. In this context, dendrimeric prodrugs may be useful. However, additional effort is required to make the costs accessible, to simplify the synthetic strategies and to investigate the behavior of cleavage. The improvement of analytical methods, purification methods and identification of synthetic products, in order to determine the physicochemical properties and bioactivity aiming to effectively implement this technology, is also required. Based on foregoing considerations, the objective of this work was to study the identity, purity and drug release of two potential dendrimeric prodrugs, based on 3-hydroxyflavone, designed to be active in leishmaniasis and Chagas disease. The first structurally contains myo-inositol as the core and branches consisting of esters from 3-hydroxyflavone with malic acid. The second structurally contains PAMAM-G0 dendrimer (initial generation polyamidoamine) as carrier and succinic acid as spacer. Suitable analytical methods for determining 3-hydroxyflavone by HPLC-UV (High Performance Liquid Chromatography) and MEKC (Micellar Electrokinetic Chromatography) have been developed. Comparing these methods, HPLC method showed more sensitivity, precision and accuracy in the quantification of 3-hydroxyflavone, while the capillary electrophoresis method was faster and less expensive. The ester of 3-hydroxyflavone with malic acid showed to be unstable in organic and aqueous solutions, at different pH and at reaction conditions of synthetic strategies evaluated, which prevented the obtaining of dendrimer based on mio-isositol as core. Notwithstanding, PAMAM-G0 dendrimer funcionalized with 3- hydroxyflavone was synthesized, purified and characterized successfully. There were no 3- hydroxyflavone releases from this dendrimer in simulated gastric fluid (pH 1.2) and a slow release was observed in buffer solutions with pH between 5.0 and 8.5, at 37.0 ºC. Submitted to biological assays in amastigotes of two strains of T. cruzi, Y(Curitiba) and Y(SS), compared to benznidazole e nifurtimox, PAMAM-G0-SUCC-3-OH-FLAV showed moderated activity and low selectivity index.
28
Fuchs, Sabine. "Oberflächenfunktionalisierte Poly(amidoamin)-Dendrimere als potentielle Trägermoleküle für Cytostatika Synthese, in vitro Cytotoxizität und intrazelluläre Verteilung /." [S.l.] : [s.n.], 2004. http://www.diss.fu-berlin.de/2004/99/index.html.
29
Lee, Tzu-Chien, and 李姿蒨. "Fabrication of Pigment-Based Electrowetting Display by Polyisobutylene-Amidoamine Disperants." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/72886299508749192018.
Анотація:
博士國立臺灣大學
高分子科學與工程學研究所
102
In Taiwan, the development of flat display devices has advanced the panel industry into prosperity and trend, and created an economic miracle in the past. However, this industry is facing high risk low-return investment and other related problems. By applying multi-incremental-based investment strategy and improving the manufacture processing, but results were unsatisfactory. The market price margin continues to decline. The related industries begin to evolve new directions of future industry development and seek for the next opportunity to make profit. Currently, the competition of flat panel displays will turn into fierce competition. The global community has been gradually investing on R&;D for the next generation product. Many parts of flat panel displays remain to be explored and developed in this emerging market. It is possible that we could make our display industry from a high-efficient mass manufacturer into a pioneer of smart life innovation application supplier. In this thesis, a new strategy has been taken to investigate the pigment-based colorants for the basic design in the electrowetting devices. The advantages of using pigments over dyes had been realized in the development of color filters and printing industries. We synthesized a new class of oily polyisobuytylene-functionalized derivatives as the dispersants for pigment dispersions. We also fabricated for the first time the electrowetting devices and studied the high differences, environmental-friendly issue, low-cost issue, and other critical technologies. The thesis is divided in two chapters (1) Tailoring Pigment Dispersants with Polyisobutylene Twin-Tail Structures for Electrowetting Display Application: We have designed a class of highly hydrophobic dispersants for finely dispersing carbon black and organic pigment nanoparticles in highly oily mediums. The structural design and the synthesis of polymeric dispersants with oily polyisobutylene molecular tails and multiple anchoring heads is essential for homogenizing the pigment dispersion in oil/water and subsequently exhibiting a high color resolution, suitable for EWD uses. (2) First Fabrication of Electrowetting Display by Using Pigment-in-Oil Driving Pixels: We report the first fabrication of pigment particle-based electrowetting display (EWD) by using the requisite poly(isobutylene)-imide (PIB-imide) for effectively dispersing insoluble colorant in decane/water system. The series of PIB-imide dispersants were prepared from the amidation/imidation of PIB-succinic anhydride with different hydrophobic lengths and a suitable amine. The structurally tailored dispersants by adopting the highly hydrophobic PIB tails allows the formation of homogeneous dispersion of nano-sized pigment particles in decane and clearly separated from water. The pigment dispersion at particle size of ca. 100 nm and a low viscosity of 2–3 cps was obtained and fabricated into an EWD device which was operated at AC voltage driver of 15–20 V in achieving a maximum aperture ratio of 80%. With the advantage of both fast response time and vivid color, the pigment-based EWD, stands out as a promising new option for future transparent display and serves as a critical foundation for the next-generation advanced display and electrical materials applications.
30
Lin, Yu-Sheng, and 林侑陞. "Synthesis of Peptide Conjugated Poly(amidoamine) Dendrimer as Artifical Racemerase." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/97525607925182174395.
Анотація:
碩士高雄醫學大學
醫藥暨應用化學研究所
98
Pyridoxal 5′-Phosphate (PLP) is the active member of of vitamin B6. PLP are known to perform numbers of reactivities in a variety of enzymes in which the lysine is a conserved residue for harboring PLP via Schiff base moiety. This is also known as external aldimine. During the course of reaction, the inbound substrate will form new Schiff base with PLP, and known as external aldimine. The exchange between external and internal aldimine is important for the demonstration of reactions. Base on the previous experimental results, we design a tripeptide involving lysine to modify the surface of PAMAM dendrimer for binding the Pyridoxal 5′-Phosphate. The designed peptides are Phe-Lys-X. The aromatic ring of phenylamine enhances the binding through PLP by?n???{???ninteraction. By the same reason, histidine, tryptophan, or tyrosine are chosen to be the third residue. During the synthesis of peptide, we found the protecting group is crucial to the solubility of those tripeptides. Those with Fmoc protecting group exhibit poor solubility. (G; 4, 5, 7)-dendri-PAMAM-(APO-Phe-Lys)n was selected for the investigation of rasemization. Under basic condition, the racemization was monitered by HPLC analysis. This result proves the ability of those synthetic dendrimers as catalyst of racemization.
31
Chen, Sih-Han, and 陳思翰. "The influence of surface electricity on internalization of Poly (amidoamine) dendrimers." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/69947244789927779824.
Анотація:
碩士國立臺灣大學
醫學工程學研究所
96
Dendrimers are highly branched polymer with high density of surface functionality and core cavities. The unique architecture of dendrimers contributes to many medical application. The surface electricity of dendrimers is defined as cationic, anionic and neutral due to the functional group, amine, carboxyl and hydroxyl. The internalization of drug/gene carriers is highly interesting because it is important for designing a suitable drug/gene carrier. In this study, several endocytotic inhibitors were used to investigate the influence of surface electricity on internalization of poly (amidoamine) (PAMAM) dendrimers, and confirmed the cellular distribution of dendrimers in the presense of various endocytotic inhibitors by confocal laser scanning microscopy. The results indicate that the cellular uptakes of different PAMAM dendrimers were obviously influenced of surface functionality on the internalizations. Cationic dendrimer was shown the highest uptake by HeLa cells, while the anionic and neutral was shown rarely enter the cells. The further studies on internalization of cationic dendrimer provide a method to investigate the detail process of the attachment and further endocytosis of particle. Understanding the internalization of dendrimers may contribute to develop the modification designing for desired applications and targeting cells.
32
Meltzer, A. Donald. "Mobility of poly(amidoamine) dendrimers; a study of NMR relaxation times." 1990. https://scholarworks.umass.edu/dissertations/AAI9022719.
Анотація:
The steric nature of the new topology created by the starburst polymer has been studied by $\sp{13}$C and $\sp2$H dynamic nuclear magnetic resonance (NMR) relaxation measurements. For two series of poly(amidoamines), PAMAM, (one OH terminated, the other NH$\sb2$ terminated), $\sp{13}$C correlation times ($\tau$) of the terminal carbons were found to be almost independent of the number of end groups; $\tau$ varied from 1.0 $\times$ 10$\sp{-11}$ to 6.3 $\times$ 10$\sp{-11}$, and no evidence of dense-packing of the end groups was observed. The $\tau$'s of the methylene carbons on the interior of the dendrimers were found to increase with molecular weight, indicative of a progressive increase in local monomer density within the polymer. No significant differences in relaxation parameters of the internal carbons were observed for the NH$\sb2$ terminated PAMAM compared to the OH terminated analogues, in either D$\sb2$O or DMSO-d$\sb6$. Thus, the results reflect topological effects, and are not due to specific solvent or end group behavior. Larger relaxation times were observed for both series when measured in D$\sb2$O. While the differences in polymer behavior in the two solvents indicate that the polymer chains are more flexible in D$\sb2$O than in DMSO-d$\sb6$, intrinsic viscosities were determined to be comparable in the two solvents (0.04-0.10 dl/g). The difference in the NMR behavior is thus attributed to strong H-bonding between the polymer and DMSO, resulting in an increase in the hydrodynamic volume of the mobile unit. The relaxation behavior of the terminal carbon, in D$\sb2$O, differed upon changing the end group. The terminal carbon of the OH terminated PAMAM was observed to be less mobile than the corresponding carbon atom in the NH$\sb2$ terminated PAMAM. $\sp2$H NMR relaxation measurements were used in a more extensive study of the mobility of amine terminated PAMAM chains as a function of molecular weight and positions. The $\tau$'s were found to increase with molecular weight, irrespective of the location of the labelling. In the last generation the $\tau$'s were found to increase as the number of termini increases from 3($\tau$ = 1.7 $\times$ 10$\sp{-12}$s) to 384 ($\tau$ = 2.2 $\times$ 10$\sp{-11}$s), and were smaller than the $\tau$'s observed when the polymers were labelled at interior positions. No significant difference in relaxation parameters was observed when the label was located in the interior repeat units, irrespective of chain length following deuteration. No evidence of radial gradients was observed.
33
Chen, Sih-Han. "The influence of surface electricity on internalization of Poly (amidoamine) dendrimers." 2008. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-3007200815240400.
34
Tsai, Ching-Hua, and 蔡靜樺. "Synthesis of Poly(amidoamine) Dendrimer with Peripheral Boronic Acid as Carbohydrates Sensor." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/897xz5.
Анотація:
博士高雄醫學大學
醫藥暨應用化學系博士班
106
Boronic acid-containing compounds have several unique features, such as strong affinity to diols and forming reversible covalent binding. The diol-containing biomolecules, such as saccharides, glycans, glycoproteins, nucleosides, are the important recognition targets in biomedical applications. Thus, boronic acid-containing compounds are important material for the selective separation and molecular recognition of diol-containing compounds. However, monoboronic acid suffers from low affinity and poor selectivity to glucose. Diboronic acid-containing compound can selectively bind glucose with well-designed geometry between two boronic acids. The poly(amidoamine) (PAMAM) dendrimers have unique advantages, such as massive number of surface groups. These features provided exclusive behavior for cooperative effect. We envisioned the cooperative effect should assist the selective binding of glucose with monoboronic acids. PAMAM dendrimers were considered as a potential platform for selective binding to glucose. We designed highly-densed boronic acid modified PAMAM dendrimer to facilitate glucose selectivity and affinity. We prepared second to sixth generation of 4-carboxyphenylboronic acid modified PAMAM dendrimers and investigated their size-dependent ability of binding to saccharides. During the preparation, we observed that phenol-modified PAMAM dendrimers formed as a hydrolysis of boronic acid, which may resulted in the difficult preoperative in the synthesis of boronic acid modified polymer. Accordingly, we found that the main factor for the hydrolysis is a massive amount of amino groups structurally closed to boronic acid. The binding affinity of 4-carboxyphenylboronic acid-modified PAMAM dendrimer with various saccharides showed that these series of PAMAM dendrimer compounds can selectively bind glucose. The binding constant of third generation 4-carboxyphenylboronic acid-modified PAMAM dendrimers (95b) with glucose is 1963.5 M-1. The 95b has the best selectivity to glucose, and its binding ability is 72.8 times, 93.6 times, and 1310 times stronger than to those of galactose, fructose and lactose respectively. To investigate the underlying mechanism, 4-carboxyphenylboronic acid-modified PAMAM dendrimer-based analogues and glucose derivatives were subjected to the binding experiments and the results indicated that boronic acids on two adjacent branches exhibit cooperative effects for binding of two sites on glucose. For the first time, 4-carboxyphenylboronic acid-modified PAMAM dendrimers exhibited highly selective bind to glucose, such as diboronic acid. So the application of dendrimer can provide different a unique recognition mode for small molecules.
35
Li, Lingling. "Rheological Properties and Reaction Kinetics of Amidoamine Oxide Surfactants-based Acids with Calcite." Thesis, 2011. http://hdl.handle.net/1969.1/ETD-TAMU-2011-05-9211.
Анотація:
A new type of viscoelastic amphoteric surfactants (amidoamine oxide) has been examined as a diverting agent during acidizing treatment. Rheological properties of viscoelastic surfactants are a function of surfactant concentration, acid additives, pH, temperature and shear rate. A HPHT rheometer was used to test the effect of common acid additives and organic acids/chelating agents on the apparent viscosity of amidoamine oxide-based acids. The compatibility and thermal stability of surfactants with corrosion inhibitor were also investigated. Rotating disk apparatus was used to examine the kinetic studies of surfactant-based acids with limestone.
The results show that the apparent viscosity of surfactant solutions prepared in deionized water, live acid, and spent acid was found to be a function of temperature. Apparent viscosity of live surfactant-based acids was also found to be a function of HCl concentration. Most of acid additives could adversely affect the rheological properties of spent acids. Compatibility tests should be done prior the field application. Cryo-TEM studies show the changes of rod-like micelle structures with the addition of additives. The reaction between surfactant-based acid and limestone was found to be mass transfer limited at 170 degrees F.
36
Hung, Wei-I., and 洪偉毅. "Synthesis and Properties of Amphiphilic Poly(amidoamine) Dendrimers with an Aniline Pentamer Shell." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/61091150965095234900.
Анотація:
博士中原大學
化學研究所
99
Poly(amidoamine) (PAMAM) dendrimers with different generations (G = 2, 3, 4 and 5) have been peripherally modified with aniline pentamers (AP). Their redox and dopable behavior are strongly affected by the dendritic architectures at different generations under different pH conditions. It was found that the electron transition of the πB–πQ band red-shifted and the size of PAMAM G2 decreased in an alkaline medium. The chemical oxidation process and the color change of these modified dendritic macromolecules were measured by cyclic voltammetry (CV) and electrochromism. All of the dendrimers showed three redox peaks in the CV. The current density of the voltammograms increased with increasing the number of aniline pentamer segments at the periphery. A drastic color change was observed when a linear potential sweep was applied. From thermal properties of the electroactive dendrimers, it reveals the introduction of electroactive AP on PAMAM dendrimers can improve the thermal stability of the dendrimers. These amphiphilic PAMAM dendrimers peripherally modified with hydrophobic AP shell can self-assemble into vesicular bilayer aggregates at lower (G2 & G3) and higher (G4 & G5) generations in water. The size of these vesicles are decrease with increasing generation under neutral pH. Critical aggregation concentration reveals that these aggregates can be favorably formed in the order of G5 ＞G4 ＞ G3 ＞ G2. These dendrimer-based vesicles are very adhesive due to the H-bonding interaction and entanglement of dendritic branches located in the outer layer. In addition, the different morphology and size of the bilayer assemblies have great influence on pH values of ~ 3, 7, and 9. The high pH form has a strongly π–π interaction between APs, whereas ion pairing at low pH leads to a loose structure of dendritic branches located in the outer layer, which can identifiable with transmission electron microscopy (TEM) images with negative staining. WAXRD experiments indicated that the higher generations of amphiphilic dendrimers are more order owing to APs exhibit a powerful driving force for the self-assembly.
37
Hartmann, Laura [Verfasser]. "Synthese monodisperser, multifunktionaler Poly(amidoamine) und ihre Anwendung als nicht-virale Vektoren für die Gentherapie / von Laura Hartmann." 2007. http://d-nb.info/983950059/34.
38
Cheng, Ming-Yu, and 鄭茗譽. "Computational study of the lowest energy conformers and spectrum of poly(amidoamine) PAMAM G0 dendrimers and it's derivative." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/24248080280367390683.
Анотація:
碩士中原大學
化學研究所
103
Understanding the dendrimer-drug interaction is of great importance to design and optimize the dendrimer-based drug delivery system. We use the lowest generation PAMAM-G0 dendrimer to study due to the time and cost . The calculated Mulliken Atomic Charges reveals the terminal group (NH2 or OH) is easy to protonated indicating that it will let the dendrimer become toxicity. Then we try to use phosphorus (P) to substitute the nitrogen (N), we found that the Mulliken Atomic Charges become more positive , indicating that it becomes less toxicity by the substitution of N to P for dendrimer. For the second part we study the interaction between dendrimer and transition metal . We consider six configurations . Our calculation show that metal is likely to bind at the core site , and the binding energy of the metal ions have the following trend Cu > Ag > Au.
39
Hung, Chih-Bing, and 洪誌彬. "Morphology and Physical Properties Studies of Porous Poly(methyl methacrylate) Composite Membranes by Incorporating Different Loading and Generation of Poly(amidoamine) Dendrimers." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/27349764031822405947.
Анотація:
碩士中原大學
化學研究所
99
In this paper, porous composite membranes were prepared via blending different generations of poly(amidoamine) (PAMAM) dendrimers with poly(methyl methacrylate) (PMMA). Phase behavior and physical properties resulted from interactions between blend components was studied, Moreover, potential application in thermal insulation materials and gas separation membranes were also investigated. First of all, a series of PAMAM dendrimers (G0 and G1) products were prepared through repeat the synthesis steps of michael addition and ester amidation. It has different sizes and different number of functional groups terminated. The as-synthesized PAMAM dendrimers were characterized by FTIR, liquid NMR and mass spectrometry (TOF-mass). PMMA with weight molecular weight (Mw) of ~ 18,000 was prepared by emulsion polymerization, then different loading and different generations of PAMAM dendrimers were blending into as-synthesized PMMA to give a series of PMMA composite membranes. Optical properties, phase behavior, thermal stability and mechanical strength of free-standing porous PMMA composite membranes was investigated by UV-visible absorption spectroscopy, SEM, DSC, TGA and DMA. It should be noted that the free-standing PMMA composite membranes exhibited good thermal insulation and gas separation based on the transient plane source (TPS) technique and gas permeability analysis (GPA) measurements, respectively.
40
Dietrich, Sascha. "(Metallo-)Dendrimers in Catalysis, Nanoparticle Stabilization and Biological Application." Doctoral thesis, 2011. https://monarch.qucosa.de/id/qucosa%3A19636.
Анотація:
(Metallo-)Dendrimers in Catalysis, Nanoparticle Stabilization
and Biological Application
Technische Universität Chemnitz, Fakultät für Naturwissenschaften
Dissertation 2011, 165 Seiten
Die vorliegende Dissertationsschrift befasst sich mit der Darstellung, Charakterisierung und Anwendung neuartiger (Metallo-)Dendrimere. Den Schwerpunkt der Arbeit bildet dabei die terminale Funktionalisierung (Poly)amidoamin-basierender Dendrimere kleiner Generationen.
Durch Standardpeptid-Knüpfungsreaktionen von 1,1´-(Diphenylphosphino)ferrocen-carbonsäure an dendritische (Poly)amidoamine ist eine Serie entsprechend funktionalisierter Metallodendrimere zugänglich. Die metallorganischen, Dendrimer-immobilisierten Engruppen können durch Zugabe von [Pd(3-C3H5)Cl]2 in heterobimetallische Übergangsmetallkomplexe umgewandelt werden und finden Einsatz als katalytisch aktive Systeme in C,C-Kreuzkupplungsreaktionen nach Heck.
Ein weiterer Gegenstand der Arbeit ist die terminale Modifikation von (dendritischen) Ami-nen mit (Sp)-2-(Diphenylphosphino)ferrocen-1-carbonsäure. Nach erfolgter Umsetzung mit [Pd(3-C3H5)Cl]2 werden die erhaltenen planar-chiralen Verbindungen als Katalysatoren in asymmetrischen allylischen Substitutionsreaktionen eingesetzt.
Ferner ist die Darstellung (Oligo)ethylenglykolether-terminierter (Poly)amidoamin-Dendrimere beschrieben. Diese werden als Stabilisatoren zur in-situ Generierung von Gold- sowie Magnetit-Nanopartikeln eingesetzt. Der Einfluss der dendritischen Template auf die Kolloidgrößen und Morphologien sowie die Eigenschaften der gebildeten Hybridmaterialien werden aufgezeigt.
Darüber hinaus befasst sich die Arbeit mit der Verwendung biokompatibler (Oligo)ethylenglykolether-Dendrimere als Wirkstoffträger für Zytostatika bei der Krebsthera-pie. Die im Rahmen von in vitro Untersuchungen erhaltenen Ergebnisse werden präsentiert.:Table of Contents
Bibliografische Beschreibung und Referat ii
Selbstständigkeitserklärung iii
Table of Contents vii
List of Abbreviations xi
Präambel xvi
A Introduction 1
1. Dendrimers 1
2. Nanomaterials 4
3. References 7
B State of Knowledge 12
1. Dendrimers 12
1.1. Synthesis and Characterization 12
1.2. Functional Dendrimers 15
2. Characterization Techniques for Dendrimer-Nanomaterial Assemblies 24
3. Motivation 26
4. References 27
C Amidoamine-based Dendrimers with End-grafted Pd-Fe Units: Synthesis, Characterization and Their Use in the Heck Reaction 34
1. Introduction 34
2. Results and Discussion 35
2.1. Synthesis of Amidoamine Dendrimers 35
2.2. Synthesis of Metallo- and Selenium-Phosphine Amidoamine Dendrimers 36
2.3. Catalysis with Heterobimetallic Iron-Palladium Amidoamine Dendrimers 39
3. Conclusions 41
4. Experimental 42
4.1. Materials and Methods 42
4.2. Preparation of 2 43
4.3. Preparation of 9-Fe 43
4.4. Preparation of 5-Fe-Pd 44
4.5. Preparation of 6-Fe-Pd 44
4.6. Preparation of 7-Fe-Pd 45
4.7. Preparation of 8-Fe-Pd 46
4.8. Preparation of 9-Fe-Pd 46
4.9. Preparation of 5-Fe-Se 47
4.10. Preparation of 9-Fe-Se 48
4.11. General Procedure for the Heck-Reaction 48
5. Acknowledgement 49
6. References 49
D A Preparation of Planar-Chiral Multidonor Phosphanyl-Ferrocene Carboxamides and Their Application as Ligands for Palladium-Catalyzed Asymmetric Allylic Alkylation 52
1. Introduction 52
2. Results and Discussion 53
2.1. Syntheses and Characterization 53
2.2. Solid-State Structure of (Sp)–2 55
2.3. Catalytic Tests 57
3. Conclusions 58
4. Experimental 59
4.1. Materials and Methods 59
4.2. Preparation of Simple Amides. A General Procedure 59
4.3. Preparation of 6 61
4.4. Preparation of (Sp,Sp)–4 61
4.5. Preparation of 7 62
4.6. Preparation of (Sp,Sp,Sp)–5 62
4.7. Asymmetric Allylic Alkylation. A General Procedure 63
4.8. X-ray Crystallography 63
5. Acknowledgements 64
6. References 64
E Au Nanoparticles Stabilized by PEGylated Low-Generation PAMAM Dendrimers: Design, Characterization and Properties 68
1. Introduction 68
2. Materials and Methods 69
2.1. Synthesis of Stabilizers 69
2.2. Preparation Procedure for Gold Nanoparticles 70
3. Results and Discussion 70
3.1. Dendritic Stabilizers 70
3.2. Dendritic Stabilized Gold Nanoparticles 72
3.3. Physical and Chemical Characterization 73
4. Conclusion 79
5. Acknowledgement 80
6. Supplementary Material 80
7. References 80
F Design, Characterization and Magnetic Properties of Fe3O4-Nanoparticle Arrays Coated with PEGylated-Dendrimers 86
1. Introduction 86
2. Materials and Methods 88
2.1. Materials and Instruments 88
2.2. Synthesis Procedure for Fe3O4 Nanoparticles 89
3. Results and Discussion 91
3.1. Preparation and Characterization of Dendrimer-Surfaced Fe3O4 Nanoparticles 91
3.2. Magnetic Characterization of Dendrimer-Coated Fe3O4 Nanoparticles 96
4. Conclusion 99
5. Acknowledgement 100
6. References 100
G Dendrimer - Doxorubicin Conjugate for Enhanced Therapeutic Effects for Cancer 103
1. Introduction 103
2. Experimental Section 105
2.1. Materials and Methods 105
2.2. Synthesis of OEGylated Poly(amidoamine) Dendrimer 2 106
2.3. Cell Viability Studies 107
2.4. Doxorubicin Loading and Release 107
2.5. In Vitro Cellular Uptake of Dendrimer-DOX Conjugate 109
3. Results and Discussion 109
3.1. Drug Loading and Release 109
3.2. Surface Potential of the Dendrimer-Drug Assembly 110
3.3. Structural Analysis of Dendrimer-DOX Conjugate 111
3.4. In Vitro DOX Release Profile from Dendrimer-Drug Conjugate 114
3.5. Cell Viability Studies of the Dendrimer-DOX Conjugate 117
3.6. Cellular Uptake by the Dendrimer-DOX Conjugate 118
3.7. Protein Adsorption Studies 119
4. Conclusions 119
5. Acknowledgements 120
6. Supplementary Material 120
7. References 121
H Summary 123
1. Summary 123
2. Zusammenfassung 129
Danksagung 136
I Appendix 137
1. Appendix Chapter C 137
2. Appendix Chapter D 139
3. Appendix Chapter E 140
4. Appendix Chapter F 142
5. Appendix Chapter G 144
Lebenslauf 145
Liste der Publikationen, Vorträge und Posterpräsentationen 147
Publikationen 147
Poster 148
Vorträge 149
41
El, Sabahy Mahmoud. "Polymeric micelles as versatile carriers for drugs and nucleic acids." Thèse, 2009. http://hdl.handle.net/1866/3481.
Анотація:
Le cancer est la principale cause de mortalité au Canada. Les taxanes (e.g. le paclitaxel et le docétaxel (DCTX)) constituent des remèdes efficaces contre une série de tumeurs solides telles que les cancers du sein, du poumon et de l’ovaire. Par ailleurs, des acides nucléiques (e.g. les oligonucléotides antisens (AON) ou les petits ARN interférents (siRNAs)), capables de supprimer sélectivement certains oncogènes impliqués dans la carcinogénèse, sont actuellement étudiés pour traiter une large gamme de cancers. Bien que l’activité des taxanes et des acides nucléiques soit bien établie sur des modèles humains et/ou animaux, plusieurs aspects physico-chimiques et cliniques restent encore à améliorer. Leur solubilité limitée (pour les taxanes), leur dégradation rapide dans le sang (pour les acides nucléiques), leur élimination précoce, leur absence de sélectivité et leur toxicité envers les tissus sains sont les principaux facteurs limitant leur efficacité. C’est pourquoi de nombreux efforts ont porté sur l’élaboration de systèmes de vectorisation ciblés à base de polymères, dans le but de surmonter les problèmes associés aux thérapies actuelles. Dans cette thèse, deux types de micelles polymères ont été développés pour la vectorisation de DCTX et d’acides nucléiques. D’une part, des micelles de poly(oxyde d’éthylène)-bloc-poly(oxyde de butylène/styrène) ont été étudiées pour la première fois pour solubiliser le DCTX et le protéger de l’hydrolyse. Ces polymères se sont révélés moins toxiques que le surfactant utilisé commercialement pour solubiliser le DCTX (i.e. polysorbate 80) et ont permis une libération prolongée du principe actif. D’autre part, deux systèmes différents de micelles polyioniques (PICM) ont été mis au point pour la vectorisation d’acides nucléiques. De nouveaux conjugués de poly(éthylène glycol) (PEG)-oligonucléotide ont été proposés pour la protection et la libération contrôlée d’AON. Lorsque ces conjugués ont été formulés avec des dendrimères de poly(amidoamine) (PAMAM), des complexes de taille homogène ont été obtenus. Ces PICM ont permis de prolonger la libération de l’AON et de le protéger efficacement contre la dégradation enzymatique. De plus, des polymères de poly(oxyde d’éthylène)-bloc-poly(méthacrylate de propyle-co-acide méthacrylique) ont été incorporés afin de conférer des propriétés acido-sensibles aux PICM. Dans ces micelles, formées de ce dernier polymère formulé avec le dendrimère PAMAM, des oligonucléotides (AON et siRNA) ciblant l’oncogène Bcl-2 ont été encapsulés. L’internalisation cellulaire fut assurée par un fragment d’anticorps monoclonal (Fab’) situé à l’extrémité de la couronne de PEG. Après l’internalisation cellulaire et la protonation des unités d’acide méthacrylique sous l’effet de l’acidification des endosomes, les micelles se sont affranchies de leur couronne. Elles ont ainsi exposé leur cœur composé d’acide nucléique et de dendrimère PAMAM, qui possède une charge positive et des propriétés endosomolytiques. En effet, ces PICM acido-sensibles ciblées ont permis d’augmenter la biodisponibilité des acides nucléiques vectorisés et se sont avérées plus efficaces pour silencer l’oncoprotéine Bcl-2 que les micelles non ciblées ou que le dendrimère de PAMAM commercial seul. Finalement, les nanovecteurs polymères présentés dans cette thèse se révèlent être des systèmes prometteurs pour la vectorisation des anticancéreux et des acides nucléiques.Cancer is considered as the leading cause of premature death in Canada. Taxanes (e.g. paclitaxel and docetaxel (DCTX)) are effective against a range of solid tumors including breast, lung, and ovarian malignancies. In addition, nucleic acids (e.g. antisense oligonucleotides (AON) and short interfering RNA (siRNA)) which are capable of selectively suppressing oncogenes involved in carcinogenesis are currently being investigated for the treatment of a wide variety of cancers. Although the activity of taxanes and nucleic acid drugs is well-established in human and/or animal models, several physicochemical and clinical issues still need to be addressed. Low aqueous solubility (i.e. taxanes), rapid degradation in the blood (i.e. nucleic acids), fast clearance, non-selectivity and toxicity to normal tissues are limiting factors to their effectiveness. Hence, many efforts have been focused on developing targeted polymeric delivery systems to overcome the problems associated with the current therapies. In this thesis, two types of polymeric micelles have been developed for the delivery of DCTX and nucleic acids. On the one hand, poly(ethylene oxide)-block-poly(butylene oxide/styrene oxide) micelles were tested for the first time to solubilize and protect DCTX from hydrolytic degradation. The polymers showed less toxicity than the surfactant used commercially to dissolve DCTX (i.e. polysorbate 80) and released the drug in a sustained fashion. On the other hand, two different systems of polyion complex micelles (PICM) were developed for the sustained release and intracellular delivery of nucleic acids. Novel poly(ethylene glycol) (PEG)-oligonucleotide conjugates were assessed to protect AON against degradation and release them in a sustained manner. When these conjugates were mixed with poly(amidoamine) (PAMAM) dendrimers, monodisperse PICM were formed. These PICM further slowed down AON release and significantly protected it against enzymatic degradation. In addition, the incorporation of poly(ethylene oxide)-block-poly(propyl methacrylate-co-methacrylic acid) was exploited to impart pH-sensitivity to PAMAM-based PICM. This system was composed of the previous copolymer mixed with PAMAM dendrimer. Such PICM were loaded with AON or siRNA targeting the Bcl-2 oncogene. Micelles uptake by the cancer cells was mediated by a monoclonal antibody fragment (i.e. Fab') positioned at the extremity of the PEG corona. Upon cellular uptake and protonation of the methacrylic acid units in the acidic endosomal environment, the micelles lost their corona, thereby exposing their positively-charged endosomolytic PAMAM/nucleic acid core. The targeted, pH-sensitive PICM were found to increase the intracellular bioavailability of the entrapped nucleic acids and knock down the Bcl-2 oncoprotein more than either non-targeted micelles or commercial PAMAM dendrimers. The polymeric nanocarriers reported in this thesis appear to be promising vehicles for the delivery of anticancer drugs and nucleic acids.
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Fuchs, Sabine [Verfasser]. "Oberflächenfunktionalisierte Poly(amidoamin)-Dendrimere als potentielle Trägermoleküle für Cytostatika : Synthese, in vitro Cytotoxizität und intrazelluläre Verteilung / vorgelegt von Sabine Fuchs." 2004. http://d-nb.info/970870396/34.