Nanoparticulas cationicas de plga para la administración del gen de interleuquina-12 en el tratamiento del cancer de higado

Resumen

TITULO: NANOPARTICULAS CATIONICAS DE PLGA PARA LA ADMINISTRACIÓN DEL GEN DE INTERLEUQUINA-12 EN EL TRATAMIENTO DEL CÁNCER DE HÍGADO RESUMEN: CATIONIC PLGA NANOPARTICLES CARRYING THE IL-12 GENE IN THE TREATMENT OF LIVER CANCER Sonsoles Diez Goñi, Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra (Spain), 2007. Nanoparticíes have been used to deliver medicines, and have advantages such as a high stability, easy uptake in the cells by endocytosis, and targeting ability to specific tissues or organs by adsorption or coating with ligand materials at the surface of the particles. The polymer we have chosen to prepare the nanoparticles is poly (lactic-co-glycolic adic) (PLGA), which is a biodegradable and biocompatible polymer. The aim of this study is the preparation of particles with a cationic surface to improve the delivery of dna into cancer cells. For this, we prepared PLGA microparticles with an optimised water-in-oil-in-water double emulsion process, by using several types of polymers with different molecular weight (RG502, RG503, RG504, RG502H, RG752). Microparticles were characterized in terms of particle size, zeta potential, encapsulation efficiency (EE %) and release rate. Plasmid DNA extracted from PLGA microparticles preserved both, structural and functional integrity. These particles protected the plasmid DNA from digestion by deoxyribonucléase I (DNAse i). Cationic microparticles prepared with PLGA in the presence of the cationic lipid DOTAP were able to transfect efficiently liver tumor cells. Finally, specific targeting to the liver has been achieved by using ligands that bind the asialoglycoprotein receptor (ASGPr), which is uniquely present on hepatocytes in a large number with high-affinity binding. As in this study, one approach has been to introduce DNA into cells by attaching it to a ligand and exploiting the natural specificity of receptor-mediated endocytosis. Asialofetuin was added as ligand to the particles which led to an increase of the level of transfection. Our results indicate that AF-nanoparticles always mediate higher gene expression compared to plain particles in the presence of serum in vitro and in the liver in vivo, and they show antitumoral activity in subcutaneous tumors in vivo.