Les microsphères d'embolisation, apparues dans les années 2000, sont des dispositifs médicaux dirigées contre les tumeurs hépatiques non opérables. Elles sont calibrés et peuvent être chargées en anticancéreux. Ces avancées majeures permettent de contrôler le niveau d'occlusion et la concentration en principe actif à injecter dans la tumeur. Cependant, le type, la taille des microsphères ou encore la concentration en anticancéreux varient d'un centre à un autre et d'un pays à un autre. Notre travail vise à comparer, sur des modèles de tumeurs hépatiques, les propriétés d'élution et l'efficacité antitumorale de différentes préparations de microsphères. La microspectroscopie infrarouge est utilisée pour mesurer la quantité de doxorubicine présente dans les microsphères à différents délais alors que la microspectrofluorimétrie permet d'évaluer la concentration et la distribution de la doxorubicine autour des billes. L'évaluation de l'activité antitumorale du traitement est mesurée sur les images spectrales infrarouge grâce à un modèle de prédiction et confirmée par un examen histopathologique. Les résultats ont montré que la vitesse d'élution dépend des propriétés physicochimiques de la microsphère, de sa taille et de la concentration de chargement. Les concentrations tissulaires de doxorubicine mesurées induisent une réduction significative de la viabilité tumorale. Le model de prédiction est un outil robuste et précis pour évaluer les modifications tissulaires. Ces résultats permettent de formuler des hypothèses mécanistiques sur l'activité antitumorale de différentes préparations de microsphères afin d'optimiser leur utilisation dans une stratégie thérapeutique clinique. / Transarterial chemoembolization is the most common treatment for patients with unresectable liver tumors. Calibrated drug eluting beads offer the advantages of controlling the level of occlusion, the amount of drug delivered, and the duration of drug delivery to the tumor. However, optimal procedure still remains unanswered and treatments differ through the use of various beads sizes or dose of loading. Our work is to compare, on experimental liver tumor model, the release properties and antitumor effects for different preparations of doxorubicin eluting beads. The amount of drug retained inside the beads, at different time point, is assessed by infrared microspectroscopy. Doxorubicin concentration and distribution in the tissue are determined by microspectrofluorimetry. Tissue modifications are quantified by a prediction model on infrared images and compared with the conventional pathological examination of stained tissue sections. Results show that elution rate of doxorubicin depend on the beads composition, the size and the loaded concentration. The doxorubicin tissue concentration induces a significant decrease of tumor viability. The prediction model established by infrared microspectroscopy is an accurate and robust tool to quantify tissue modifications. These results allow the formulation of mechanistic hypotheses on antitumor activity of different preparations of beads to optimize their use in a clinical therapeutic strategy.

The aim of this diploma thesis is the application of vibrational spectroscopy in pharmaceutical analysis in studying solid pharmaceutical forms. The surface of tablet samples containing the active substance from the group of statins has been studied especially by the methods infrared microscopy. Spectral maps of samples were collected thanks to the techniques of specular reflection, attenuated total reflection (ATR) and "inverse" ATR after determining optimal conditions for measurements. In order to evaluate these measured maps, one-dimensional analysis and principal component analysis were used. As the same samples of tablets were also measured by Raman microscopy, the comparison has been provided. The measured distribution maps enable both a determination of substances in the sample and conclusion concerned a method of tablets' preparation. The method in this case is a granulation, which has been found out from a comparison of maps of generic and original medicament. The specular reflection method was selected to be the most appropriate technique for obtaining the maps of the surface of a tablet, via confrontation of particular methods consequently with consideration of their advantages and disadvantages in the measurement and data processing.