Vecteurs microparticulaires adhesifs specifiques des selectines (French text)

A new active microparticulate polymeric vector targeting the inflammatory endothelial cell surface E-selectins was developed. These vectors could be used for the treatment of diseases with an inflammatory component such as rheumatoid arthritis and cancer. A drug with a narrow therapeutic index could then be delivered at its site of action. The introduction presents a recent literature review on the subject: drug targeting; applications, fabrications and characterization of micro- and nanoparticles; cell-adhesion; and adhesion molecules. A new branched polymer family was developed to make pharmaceutical vectors. These polyesters are copolymers of hydroxy-acids and allyl glycidyl ether allyl-, hydroxyl- and carboxyl-derivatives. The results presented allowed the rapid and easy production of allyl-, hydroxyl- and carboxyl-branched hydrolysable polymers. A new synthesis for the preparation of a known potent E-selectin ligand is also presented. The new approach allowed the binding of this molecule to one of the developed polymers. A new microparticulate vector was prepared from this specific polymer. Blind ex vivo assays with rat mesenteric veins showed quantitatively the strong adhesion of this vector to inflammatory endothelial cells. Globally, this thesis presents research results in the field of cellular adhesion receptor drug targeting from medicinal chemistry to conclusive ex vivo assays.