Tout ce qui vit, naît, se nourrit, se reproduit et meurt. Pour le cerveau, la question se complexifie car à la survie des neurones s'ajoute le coût de l'activité cérébrale. La question de la gestion énergétique pour les neurones est particulière car les cellules de notre cerveau évoluent de manière concertée et non par compétition. On sait avec l'imagerie médicale que l'usine neuronale ne fonctionne pas uniquement grâce au glucose ; elle utilise d'autres apports énergétiques tels que le lactate ou le glutamate pour soutenir sa production. Lorsqu'une tumeur apparaît, elle change le métabolisme énergétique pour survivre et soutenir sa propre croissance. En particulier, les cellules cancéreuses se fournissent en lactate et choisissent leur substrat préféré en fonction de l'oxygène disponible. La modélisation mathématique des substrats énergétiques est un outil de choix pour décrire et prédire de tels flux. Coupler ces modèles à des données issues de l'IRM et de la SRM permet d'améliorer la prise en charge du patient présentant un gliome.Cette thèse propose l'approche de plusieurs dynamiques en substrat dans le cerveau sain et gliomateux en se basant sur des systèmes d'équations : échanges locaux en lactate (EDO, système lent-rapide), échanges globaux en substrats (EDO), cycle glutamate/glutamine (EDR) et échanges en lactate en dimensions supérieures (EDP). Ces modèles sont expliqués, décrits grâce aux mathématiques et permettent l'élaboration de simulations ajustées selon des données patient ou issues de la littérature.L'énergie est nécessaire au maintien de la vie. Mais si votre voisin consomme une partie de vos ressources, pouvez-vous encore espérer survivre ? / Everything that lives is born, eats, reproduces and dies. For the brain, the question is more complex because neurons have to survive and to support brain activity. Energy management is also particular because brain cells evolve together with no competition. Thanks to medical imaging, we know that neurons do not consume only glucose. They can use others energetic substrates such as lactate and glutamate as a power source.When a tumor appears, it changes the energetic metabolism to survive and support its own growth. In particular, cancer cells like to consume lactate. They also choose their favorite substrate based on the available oxygen. Modeling of energy substrates is useful to describe and predict energetic kinetics and changes. Mathematical models could get with clinical and medical results to describe, explain or predict low grade glioma dynamics. They can help to characterize and quantify a tumor evolution, then leading to improve their therapeutical management. Exchanges between mathematics and MRI (and MRS) enable to get accurate data and to build suitable mathematical models.This thesis deals with several approaches of substrates dynamics in healthy and gliomatous brains. These researches are based on systems of equations. We model local lactate exchanges (ODE, fast-slow systems), global substrates exchanges (ODE), glutamate/glutamine cycle (RDE) and local lactate exchanges in higher dimensions (PDE). We describe, analyze and give simulations of these models. Simulations are fitted on patient MRI data or literature data. Energy is necessary to live. But if your neighbor consumes a part of your resources, can you still survive ? / Tutto ciò che vive nasce, si nutre, si riproduce e muore. Per il cervello, la questione è più complessa perché i neuroni devono sopravvivere e sostenere l'attività cerebrale. La gestione energetica cerebrale è particolare anche perché le cellule cerebrali evolvono insieme, senza concorrenza. Inoltre, grazie alle immagini mediche, sappiamo che i neuroni non consumano solo del glucosio ma usano altri substrati energetici come il lattato o il glutammato.Quando un tumore si stabilisce, cambia il metabolismo energetico del cervello per sopravvivere e sostenere la propria crescita. In particolare, cellule tumorali consumano del lattato e scelgono il loro substrato preferito basandosi all'ossigeno disponibile.La matematica, e in particolare l'elaborazione di modelli matematici può aiutarci a ottimizzare i dati disponibili, che possono essere, di volta in volta, delle proprietà cellulare o delle lastre MRI o MRS. La modellizzazione dei substrati energetici potrebbe descrivere, spiegare o prevedere le dinamiche energetiche nel cervello.Questa tesi tratta di diversi approcci della dinamica dei substrati nei cervelli sani e gliomatosi. Queste ricerche si basano su sistemi di equazioni. Modellizziamo scambi locali di lattato (ODE, sistemi fast-slow), scambi globali di substrati (ODE), ciclo glutammato/glutammina (RDE) e scambi locali di lattato in dimensioni superiori (PDE). Descriviamo, analizziamo e diamo simulazioni di questi modelli. Le simulazioni sono adeguate su dati MRI paziente o dati di letteratura.Per vivere, l’energia è una necessità. Ma se i Suoi vicini consumassero le Sue risorse, riuscirebbe ancora a sopravvivere ?

De nombreux changements cérébraux s’opèrent au cours du vieillissement normal, et ce, tant au niveau structurel que fonctionnel. Ces changements résultent le plus souvent en une certaine détérioration du fonctionnement cognitif et se répercutent ainsi sur la qualité de vie des personnes âgées. Il appert toutefois que certaines personnes se voient relativement épargnées et parviennent à maintenir un niveau de fonctionnement cognitif comparativement élevé en dépit de l’avancement en âge. En présence d’une accélération du vieillissement populationnel, il devient donc criant de comprendre les facteurs et les mécanismes neurobiologiques qui contribueraient à cette meilleure résilience face aux effets du vieillissement sur le cerveau et la cognition. Bien que plusieurs modèles aient tenté de rendre compte de ce phénomène, la compréhension des mécanismes qui le sous-tendent demeure à ce jour relativement lacunaire. L’objectif principal de cette thèse était ainsi d’exposer les corrélats neurobiologiques associés à une meilleure résilience face aux effets du vieillissement normal sur le cerveau et la cognition, et ce, par l’entremise de mesures d’imagerie par résonance magnétique structurelle (IRM) et fonctionnelle (IRMf). Cette thèse contient quatre articles. L’intention du premier article (Chapitre II) était de faire une synthèse des connaissances quant aux mécanismes impliqués dans la résilience contre les effets délétères du vieillissement normal sur la cognition. Dans cette revue de la littérature, nous nous sommes intéressés à deux des principaux modèles visant à rendre compte de ce phénomène de protection : la réserve cérébrale et la réserve cognitive. L’examen de la littérature empirique amène à la conclusion qu’une meilleure résilience pourrait reposer sur des différences cérébrales à la fois structurelles et fonctionnelles, et donc que les deux modèles proposés pourraient amener une contribution indépendante au phénomène de résilience. Par ailleurs, nous soulevons l’hypothèse que les corrélats de la résilience s’apparentent grandement aux différences cérébrales associées aux entraînements cognitifs. Les trois articles suivants sont des articles empiriques qui s’intéressent à la mémoire de travail, une fonction qui décline avec l’âge, mais qui montre d’importantes différences interindividuelles. L’objectif du second article (Chapitre III) était d’investiguer la relation entre la scolarité, un indicateur de réserve (reserve proxy) bien établi, et le volume régional de la substance grise, ainsi qu’entre la scolarité et les activations cérébrales lors d’une tâche de mémoire de travail chez des participants âgés et cognitivement sains. Les résultats indiquent qu’un nombre d’années de scolarité plus élevé est à la fois associé à une moindre perte de volume liée à l’âge dans les régions frontales et pariétales, ainsi qu’à une plus grande activation liée à l’âge dans certaines régions préfrontales faisant partie du réseau de la mémoire de travail. La troisième étude (Chapitre IV) visait à examiner si les différences cérébrales fonctionnelles associées à la scolarité sont compatibles avec des mécanismes d’efficacité ou de flexibilité neuronale. Elle avait ensuite pour objectif d’examiner l’effet « protecteur » de ces différences fonctionnelles sur le plan de la performance en mémoire de travail. Les résultats suggèrent que les deux mécanismes posés seraient associés à une meilleure préservation de la mémoire de travail face aux effets de l’âge, mais que leur implication respective dépendrait du niveau d’exigence de la tâche. Enfin, l’objectif de la quatrième étude (Chapitre V) était de tester, dans un premier temps, la relation entre l’engagement dans un style de vie stimulant et le maintien de l’intégrité de la substance blanche. Puis, l’étude visait dans un second temps à examiner si une plus grande intégrité de la substance blanche diminuait l’impact de l’âge sur la mémoire de travail. Les résultats de l’étude suggèrent qu’un style de vie plus stimulant serait associé à un moindre volume de lésions de la substance blanche liées à l’âge et que ce moindre volume de lésions de la substance blanche serait en retour associé à de meilleures performances en mémoire de travail. / Many changes to the brain occur in normal aging, both structurally and functionally. These changes most often result in a certain deterioration of cognitive functioning, and thus affect the quality of life of the elderly. It appears, however, that some people are relatively spared and manage to maintain a comparatively high level of cognitive functioning despite advancing in age. In the presence of an acceleration of population aging, there is a striking need to understand the factors and neurobiological mechanisms that may contribute to this better resilience to the effects of aging on the brain and on cognition. Although several models have attempted to account for this phenomenon, the understanding of the mechanisms that underpin it is still relatively incomplete. The main objective of this thesis was to expose the neurobiological correlates associated with a better resilience to the effects of normal aging on the brain and cognition, through structural (MRI) and functional magnetic resonance imaging (fMRI). This thesis contains four articles. The intention of the first article (Chapter II) was to synthesize knowledge about the mechanisms involved in the resilience against the degenerative effects of normal aging on cognition. In this literature review, we were interested in the two main models attempting to account for this protective phenomenon: the brain reserve and cognitive reserve. Examining the empirical literature leads to the conclusion that better resilience might be based on both structural and functional brain differences, and therefore that the two proposed models could make an independent contribution to the resilience phenomenon. In addition, we hypothesize that the correlates of resilience are very similar to the brain differences associated with cognitive training. The following three articles are empirical articles which focus on working memory, a function that declines with age but shows significant inter-individual differences. The purpose of the second article (Chapter III) was to investigate the relationship between education, a well-established reserve proxy, and the regional volume of gray matter, as well as between education and brain activation during a working memory task in cognitively healthy elderly participants. Results indicate that higher years of education are associated with lower age-related loss of volume in the frontal and parietal areas, as well as greater age-related activation in some prefrontal regions that are part of the working memory network. The third study (Chapter IV) sought to examine whether functional education-related brain differences are compatible with neuronal efficiency and/or flexibility mechanisms. It further aimed to examine the "protective" effect of these functional differences on working memory performance. The results suggest that the two proposed mechanisms would be associated with a better preservation of working memory in the face of the effects of age, but that their respective involvement would depend on the level of the task requirement. Finally, the objective of the fourth study (Chapter V) was to first test the relationship between engagement in a stimulating lifestyle and white matter integrity maintaining. Then, the study aimed to examine whether greater white matter integrity decreased the impact of age on working memory. The results of the study suggest that a more stimulating lifestyle would be associated with a lesser age-related white matter lesions volume, and that this smaller white matter lesions volume would in turn be associated with better working memory performance.

Background: Normal pressure hydrocephalus (NPH) has been an ongoing and challenging field of research for the past decades because two main issues are still not fully understood: the pathophysiologic mechanisms underlying ventricular enlargement and prediction of outcome after surgery. Purpose: To evaluate changes in diffusion tensor imaging (DTI) derived parameters in patients with suspected normal pressure hydrocephalus before and after withdrawal of cerebrospinal fluid (CSF). Material and Methods: Twenty-four consecutive patients with clinical and radiological suspicion of NPH and 14 agematched control subjects were examined with DTI on a clinical 3T scanner. Patients were examined before and 6–36 h after CSF drainage (interval between scans, 5 days). Fifteen patients were finally included in data analysis. Fractional anisotropy (FA) and mean, parallel, and radial diffusivity (MD, PD, RD) were evaluated using a combination of a ROI-based approach and a whole-brain voxel-by-voxel analysis. Results: Alteration of DTI parameters in patients with suspected NPH is regionally different. Compared to the control group, we found an elevation of FA in the subcortical white matter (SCWM) and corpus callosum, whereas the other diffusion parameters showed an increase throughout the brain in variable extent.We also found a slight normalization of RD in the SCWM in patients after lumbar drainage. Conclusion: Our results show that DWI parameters are regionally dependent and reflect multifactorial (patho-) physiological mechanisms, which need to be interpreted carefully. It seems that improvement of gait is caused by a decrease of interstitial water deposition in the SCWM.

A polineuropatia inflamatória desmielinizante crônica (PIDC) é uma síndrome caracterizada fundamentalmente pela disfunção do Sistema Nervoso Periférico e que afeta muito a qualidade de vida dos pacientes. O envolvimento da PIDC com o Sistema Nervoso Central tem sido descrito, maiormente como sendo subclínico, porém não há estudos sobre a caracterização deste envolvimento de uma forma ampla e quantitativa. Avaliamos 11 pacientes com PIDC, todos tratados e sem sinais clínicos de alterações centrais, e 11 controles, pareados em gênero e faixa etária de 19 a 69 anos. Foram adquiridas neuroimagens em uma máquina de Ressonância Magnética de alto campo (3T) usando diferentes técnicas de imagens; volumétricas ponderadas em T1, volumétricas de inversão e recuperação com atenuação de fluidos e ponderadas em T2, relaxométricas de cinco ecos para mapas de T2, de transferência de magnetização e por tensor de difusão. As imagens foram processadas em diferentes ferramentas computacionais e foram obtidos resultados para estudos da difusibilidade, volumetria, morfometria, tratometria e conectividade cerebral, além de achados radiológicos para os pacientes. As análises de grupos foram executadas por; 1) testes paramétricos monocaudais de duas amostras pareadas para os resultados da volumetria, da tratometria e conectividade cerebral; 2) mapeamento estatístico paramétrico para os resultados da morfometria baseada em voxel e; 3) estatística espacial baseada em tratos para os resultados da difusibilidade. Foram detectas alterações em todas as comparações. Os principais achados indicam um envolvimento possivelmente caracterizado por uma perda volumétrica encefálica generalizada, sobretudo nas regiões periventriculares associadas a ventrículos proeminentes acrescido de, um aumento da difusibilidade transversa e oblíqua nos maiores tratos de substância branca e, também há uma perda de densidade na substância branca periventricular e um aumento na substância cinzenta em uma região que sinaliza para o espessamento trigeminal bilateral e, uma redução geral da conectividade cerebral estrutural. / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a severe disease fundamentally characterized by dysfunction of the Peripheral Nervous System and affects greatly the quality of life of patients. The Central Nervous System (CNS) involvement in CIDP has not been described using recent quantitative neuroimaging techniques. We evaluated 11 patients with CIDP, all treated and without clinical signs of central alterations and 11 controls matched for gender and age group of 19 to 69 years. Magnetic Resonance Imaging were performed on a 3T scanner using different imaging techniques; structural 3D T1-weighted, fluid-attenuated inversion recovery, relaxometry with 5 echoes pulse sequence for T2 maps, magnetization transfer weighted and diffusion tensor imaging. The images were processed on different tools and were obtained results for the studies of diffusivity, volumetry, morphometry, tractometry, brain connectivity, and radiological findings of patients. Different statistical group analyses were performed in the quantitative results: 1) Parametric test for volumetry, tractometry and brain connectivity; 2) Parametric mapping for voxel morphometry; 3) Tract-based spatial statistics (TBSS) for diffusion coefficients. Changes were detected in all comparisons. In the patients, our main findings are: generalized loss brain volume more pronounced in periventricular regions associated with prominent ventricles, increased simultaneously perpendiculars and parallel diffusivity in the major tracts of the TBSS analyze, white matter density loss in the periventricular area, some bilateral trigeminal thickening, and general reduction of the brain connectivity. The CIDP affects the global brain and represents a demyelination in the CNS.

A polineuropatia inflamatória desmielinizante crônica (PIDC) é uma síndrome caracterizada fundamentalmente pela disfunção do Sistema Nervoso Periférico e que afeta muito a qualidade de vida dos pacientes. O envolvimento da PIDC com o Sistema Nervoso Central tem sido descrito, maiormente como sendo subclínico, porém não há estudos sobre a caracterização deste envolvimento de uma forma ampla e quantitativa. Avaliamos 11 pacientes com PIDC, todos tratados e sem sinais clínicos de alterações centrais, e 11 controles, pareados em gênero e faixa etária de 19 a 69 anos. Foram adquiridas neuroimagens em uma máquina de Ressonância Magnética de alto campo (3T) usando diferentes técnicas de imagens; volumétricas ponderadas em T1, volumétricas de inversão e recuperação com atenuação de fluidos e ponderadas em T2, relaxométricas de cinco ecos para mapas de T2, de transferência de magnetização e por tensor de difusão. As imagens foram processadas em diferentes ferramentas computacionais e foram obtidos resultados para estudos da difusibilidade, volumetria, morfometria, tratometria e conectividade cerebral, além de achados radiológicos para os pacientes. As análises de grupos foram executadas por; 1) testes paramétricos monocaudais de duas amostras pareadas para os resultados da volumetria, da tratometria e conectividade cerebral; 2) mapeamento estatístico paramétrico para os resultados da morfometria baseada em voxel e; 3) estatística espacial baseada em tratos para os resultados da difusibilidade. Foram detectas alterações em todas as comparações. Os principais achados indicam um envolvimento possivelmente caracterizado por uma perda volumétrica encefálica generalizada, sobretudo nas regiões periventriculares associadas a ventrículos proeminentes acrescido de, um aumento da difusibilidade transversa e oblíqua nos maiores tratos de substância branca e, também há uma perda de densidade na substância branca periventricular e um aumento na substância cinzenta em uma região que sinaliza para o espessamento trigeminal bilateral e, uma redução geral da conectividade cerebral estrutural. / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a severe disease fundamentally characterized by dysfunction of the Peripheral Nervous System and affects greatly the quality of life of patients. The Central Nervous System (CNS) involvement in CIDP has not been described using recent quantitative neuroimaging techniques. We evaluated 11 patients with CIDP, all treated and without clinical signs of central alterations and 11 controls matched for gender and age group of 19 to 69 years. Magnetic Resonance Imaging were performed on a 3T scanner using different imaging techniques; structural 3D T1-weighted, fluid-attenuated inversion recovery, relaxometry with 5 echoes pulse sequence for T2 maps, magnetization transfer weighted and diffusion tensor imaging. The images were processed on different tools and were obtained results for the studies of diffusivity, volumetry, morphometry, tractometry, brain connectivity, and radiological findings of patients. Different statistical group analyses were performed in the quantitative results: 1) Parametric test for volumetry, tractometry and brain connectivity; 2) Parametric mapping for voxel morphometry; 3) Tract-based spatial statistics (TBSS) for diffusion coefficients. Changes were detected in all comparisons. In the patients, our main findings are: generalized loss brain volume more pronounced in periventricular regions associated with prominent ventricles, increased simultaneously perpendiculars and parallel diffusivity in the major tracts of the TBSS analyze, white matter density loss in the periventricular area, some bilateral trigeminal thickening, and general reduction of the brain connectivity. The CIDP affects the global brain and represents a demyelination in the CNS.

Η Πακλιταξέλη (PTX) αποτελεί ένα ευρέως διαδεδομένο αντινεοπλασματικό φάρμακο και ενδείκνυται σε μεταστατικό καρκίνο του μαστού, καρκίνο ωοθηκών, μη μικροκυτταρικό καρκίνο του πνεύμονα και σε σάρκωμα Kaposi ασθενών με AIDS. Παρ’ όλα αυτά, η σημαντική τοξικότητα που εμφανίζει (μυελοκαταστολή, νευροτοξικότητα, αντιδράσεις υπερευαισθησίας), υπογραμμίζει την αναγκαιότητα για μορφοποίησή της σε Συστήματα Ελεγχόμενης Χορήγησης Φαρμάκων (DDS), με σκοπό τη μείωση των ανεπιθύμητων ενεργειών και την αύξηση της βιοδιαθεσιμότητας του φαρμάκου. Τα πολυμερικά μικκύλια έχουν μελετεθεί εκτενώς τα τελευταία χρόνια ως Συστήματα Ελεγχόμενης Χορήγησης Φαρμάκων. Η ενσωμάτωση υπερπαραμαγνητικών νανοκρυσταλλιτών οξειδίου του σιδήρου (SPIONs) στον πυρήνα των PTX-μικκυλίων, παρέχει τη δυνατότητα μαγνητικής στόχευσης του φαρμάκου στην επιθυμητή περιοχή δράσης, καθώς και τη θεραπεία του καρκίνου μέσω επαγωγής μαγνητικής υπερθερμίας, με την εφαρμογή εναλλασσόμενου μαγνητικού πεδίου. Επιπλεόν, η χρήση των SPIONs ως σκιαγραφικά μέσα (Τ2-contrast enhancement) στη μαγνητική τομογραφία πυρηνικού συντονισμού (MRI), εξασφαλίζει το πλεονέκτημα ταυτόχρονης διάγνωσης και θεραπείας (Theranostics), αποκαλύπτοντας την πολυλειτουργικότητα των συστημάτων αυτών. Οι συγκεκριμένοι νανοφορείς, έχοντας μικρό μέγεθος (100-200nm), θεωρούνται κατάλληλοι για να αποφύγουν την οψωνινοποίηση απο τις λιποπρωτεϊνες του αίματος, την επίθεση απο τα φαγοκύτταρα του Δικτυοενδοθηλιακού συστήματος (RES) καθώς και την ταχεία νεφρική κάθαρση, με αποτέλεσμα την παρατεταμένη κυκλοφορία τους στο αίμα (stealth systems) και την εκλεκτική πρόσληψη τους απο τους συμπαγείς καρκινικούς όγκους, μέσω του φαινομένου της ενισχυμένης διαπερατότητας και κατακράτησης (EPR effect). Οι ιδιότητες αυτές, καθιστούν τα συγκεκριμένα συστήματα πολύτιμα εργαλεία στον τομέα της νανοϊατρικής. Η παρούσα μεταπτυχιακή διατριβή πραγματεύεται τη σύνθεση υδρόφοβων SPIONs μέσω της τεχνικής της θερμικής αποικοδόμησης. Μελετήθηκαν οι συνθετικές παράμετροι (πρόδρομη ένωση, ποσότητα ελαϊκού οξέος, θερμοκρασία και διάρκεια αντίδρασης, ρυθμός αύξησης της θερμοκρασίας κ.α) που επηρεάζουν το μέγεθος, το σχήμα και τη διασπορά του μεγέθους των σχηματιζομένων νανοκρυσταλλιτών (5-13nm, σ: 10-20%), καθώς διαδραματίζουν σημαντικό ρόλο στη μαγνητική συμπεριφορά των υβριδικών νανονοφορέων. Στη συνέχεια, πραγματοποιήθηκε σύνθεση υβριδικών νανοφορέων με εγκλωβισμό των SPIONs σε πολυμερικά μικκύλια. Η παρασκευή των υπερπαραμαγνητικών μικκυλίων επιτελέστηκε με την τεχνικη solvent diffusion and evaporation (nanoprecipitation), με χρήση του αμφίφιλου συμπολυμερούς πολυ(γαλακτικό οξύ)-πολυ(αιθυλενογλυκόλη) (PLA-PEG). Στον υδρόφοβο πυρήνα των μικκυλίων (PLA) δεσμεύονται υδρόφοβες ενώσεις (PTX, SPIONs), ενώ το υδρόφιλο κέλυφος (PEG) προσδίδει κολλοειδή σταθερότητα σε υδατικά μέσα (δομή πυρήνα-κελύφους). Διερευνήθηκαν διάφορες συνθετικές παράμετροι (μοριακό βάρος συμπολυμερούς, ποσότητα SPIONs, ρυθμός προσθήκης οργανικής φάσης κ.α) και προσδιορίστηκαν οι βέλτιστες συνθήκες για την παρασκευή υπερπαραμαγνητικών μικκυλίων μεγέθους <200nm, με αξιοσημείωτη κολλοειδή σταθερότητα (μέχρι και έξι μήνες), σε συνθήκες παρόμοιες με αυτές του ανθρώπινου πλάσματος (pH: 7.4, ιοντική ισχύς: 0.15Μ). Στο επόμενο στάδιο της παρούσας εργασίας, μελετήθηκαν οι παράγοντες που επηρεάζουν τη φόρτωση-ενκαψυλίωση της PTX και των SPIONs στα πολυμερικά μικκύλια (ποσότητα PTX, ποσότητα και μέγεθος SPIONs, μοριακό βάρος PLA-PEG, ρυθμός προσθήκης οργανικής φάσης κ.α), σε φυσιολογικές συνθήκες (pH:7.4, ιοντική ισχύς: 0.15Μ). Αναπτύχθηκε πρωτόκολλο μέσω του οποίου έγινε κατορθωτός ο διαχωρισμός των μαγνητικών νανοφορέων απο τους μη μαγνητικούς, καθώς και ο υπολογισμός της φόρτωσης-ενκαψυλίωσης PTX και SPIONs ξεχωριστά, τόσο στους μαγνητικούς και μη μαγνητικούς νανοφορείς, όσο και στο μέιγμα αυτών. Οι συγκεκριμένοι νανοφορείς χαρακτηρίζονται απο εξαιρετικά υψηλή απόδοση ενκαψυλίωσης φαρμάκου (93 %wt.) και φόρτωση φαρμάκου που ανέρχεται στο 4.8 %wt. Oι αμιγώς μαγνητικοί νανοφορείς επιδεικνύουν υψηλή απόδοση ενκαψυλίωσης νανοκρυσταλλιτών (70 %wt.), ενώ η φόρτωση σε φάρμακο και SPIONs ανέρχεται σε 5.2 και 20 %wt. αντίστοιχα. Σε αμφότερες τις περιπτώσεις οι νανοφορείς, μεγέθους (υδροδυναμική διάμετρος) 170nm, χαρακτηρίζονται απο ικανοποιητική μαγνητική συμπεριφορά. Εξετάστηκε η επίδραση του μεγέθους των νανοκρυσταλλιτών στη μαγνητική συμπεριφορά των νανοφορέων. Οι αμιγώς μαγνητικοί νανοφορείς με μεγαλύτερο μέγεθος SPIONs παρουσιάζουν καλύτερη μαγνητική συμπεριφορά. Τέλος, πραγματοποιήθηκαν μελέτες αποδέσμευσης του φαρμάκου σε PBS (0.14Μ, pH:7.4) στους 37oC και διερευνήθηκε η επίδραση της εφαρμογής εναλλασσόμενου μαγνητικού πεδίου στην αποδέσμευση της PTX απο τους μαγνητικούς νανοφορείς (Triggered Drug Release). Σε κάθε περίπτωση, παρατηρήθηκε ελεγχόμενη αποδέσμευση του φαρμάκου για 24 ώρες, σε συνθήκες που προσομοιάζουν με αυτές του πλάσματος. Ο φυσικοχημικός χαρακτηρισμός των νανοφορέων πραγματοποιήθηκε με HPLC, DLS, TGA, TEM και μαγνητοφόρηση. / Paclitaxel (PTX) is one of the most successful anticancer drugs against a broad range of solid tumors, such as metastatic breast cancer, ovarian cancer, non-small-cell lung cancer and AIDS-related Kaposi sarcoma. However, the serious systematic side effects of PTX (myelosuppression, neurotoxicity, hypersensitivity) underline the need for formulation of PTX in Drug Delivery Systems (DDS), in order to reduce the side effects and increase the bioavailability of the drug. Among DDS, polymeric micelles have drawn much attention due to their great flexibility in tuning drug solubility, micelle size, targeted drug delivery and stability. Incorporation of Superparamagnetic Iron Oxide Nanocrystals (SPIONs) inside the core of drug-loaded polymeric micelles, imparts to the final Drug Delivery System the prospect of physical (magnetic) targeting, intrinsic therapeutic function (hyperthermia-based cancer therapy under alternating external magnetic field), T2-based contrast enhancement in magnetic resonance imaging (MRI) and remotely triggered drug release. These core-shell polymeric micelles having small size (100-200nm), are considered appropriate for avoiding both opsonization, macrophages attack by ReticuloEndothelial System (RES) and rapid renal clearance, thus allowing micelles to be taken up preferably by solid tumors through Enhanced Permeability and Retention (EPR) effect. Therefore, such nanoassemblies encode high potential in nanomedicine, due to their dual nature (Therapeutic+Diagnostic = Theranostics). In particular, we have studied the synthesis of organophilic SPIONs through thermal decomposition. The synthetic parameters (precursor, precursor:oleic acid ratio, reaction temperature and duration, heat rate, etc.) affecting the size, shape and size distribution of the nanocrystals have also been examined thoroughly, since they play a key-role concerning the magnetic behavior of the final hybrid. Nanosized SPIONs with narrow size distribution were synthesized (5-13nm, σ: 10-20%). The preparation of poly(lactic acid)-block-poly(ethyleneglycol) (PLA-PEG) micelles encapsulating hydrophobic SPIONs, by varying the molecular weight of the polymers, the amount of SPIONs and the addition rate during micelle assembly, has also been investigated. The core-shell superparamagnetic micelles were prepared through solvent diffusion and evaporation technique (nanoprecipitation). PTX and SPIONs are being incorporated into the micelle’s hydrophobic core (PLA) through hydrophobic interactions, whereas the hydrophilic shell (PEG) stabilizes the micelles in aqueous dispersions, optimizing their colloidal stability and providing prolonged circulating time. The optimum parameters were determined, conferring to the micelles (Hydrodynamic Diameter < 200nm) high colloidal stability (up to six months) at biorelevant conditions (pH:7.4, ionic strenght: 0.15M). The next phase of the present master thesis focused on studying the factors (amount of PTX and SPIONs, molecular weight of PLA-PEG, addition rate, etc.) affecting the Loading of PTX and SPIONs into the polymeric micelles and how they can be fine-tuned towards high drug loading, while retaining their size at a scale where long circulation would not be precluded. Through protocol establishment, we have managed to separate the magnetic and non magnetic micelles, and to determine individually the loading of PTX and SPIONs for magnetic, non magnetic micelles, as well as for the mixture of them. The micelles’ mixture exhibits very high Drug Encapsulation Efficiency (93 %wt.) and 4.8 %wt. Drug Loading (D.L). Magnetic nanocarriers display high Magnetic Encapsulation Efficiency (70 %wt.), with D.L and Magnetic Loading of 5.2 and 20 %wt. respectively, In both cases, micelles demonstrate adequate magnetic behavior and small sizes (hydrodynamic diameter: 170nm), under conditions which simulate with human plasma (pH:7.4, ionic strenght: 0.15M). The effect of SPIONs’ size on the magnetic behavior of hybrid colloids, was also examined. Magnetic nanocarriers encapsulating SPIONs of greater size exhibit better magnetic behavior. Finally, we have conducted Drug release studies in PBS (0.14M, pH:7.4) at 37oC. The effect of SPIONs presence on the release profile of PTX, including triggered drug-release by application of AC magnetic field, has also been investigated. PTX-magnetic micelles exhibit Controlled Drug release for 24 hours. Several techniques have been used for the characterization of such nanoassemblies, like: HPLC, DLS, TGA, TEM, XRD, Magnetophoresis and Triggered Drug release by application of AC magnetic field.