Self-assemblies of azacitidine prodrug: An innovative therapy against myelodysplastic syndromes
Résumé
5-azacitidine, a cytidine analogue and a hypomethylating agent, is one of the main drugs being used for the treatment of myelodysplastic syndromes . However after administration, it exhibits several limitations including restricted diffusion and cellular internalization due to its hydrophilicity, and rapid enzymatic degradation. Our objective is to improve the drug diffusion and to protect it from metabolic degradation via the formulation of an amphiphilic prodrug and its self-assembly into a nanoparticle. Following the conjugation of the fatty acid to the azacitidine, the obtained prodrug was solubilized in acetone and mixed with water at different ratios to obtain self-assemblies by nanoprecipitation, thus protecting the active molecule from enzymatic degradation. This prodrug should be cleaved by cathepsin B , an enzyme overexpressed in cancerous cells , thus increasing the specificity of the drug.
Origine : Fichiers produits par l'(les) auteur(s)