Nuevas formulaciones farmacéuticas basadas en la nanotecnología dirigidas al tratamiento del cáncer mediante estrategias de terapia génica

Abstract

In this project we have characterized and evaluated the in vitro and in vivo transfection efficiency of lipid/DNA (lipoplexes) and PEI 25/DNA (poliplexes), formed with the ligands transferrin and asialofetuin, and the peptide protamine. Both types of complexes were characterized showing an homogeneous particle size in the nanometer range and positive surface charge. It has been shown a good transfection efficiency of transferrin and asialofetuin formulations, and in all cases transfection further increased in the presence of ligands with protamine. In HepG2 cells (human hepatoblastoma) we have obtained the best transfection efficiency with both lipoplexes and polyplexes in the presence of asialofetuin with protamine. In HeLa cells (human cervix-uterine carcinoma) and CT-26 (murine colon carcinoma) the best results were obtained in the presence of transferrin with protamine. The toxicity of lipoplexes was much lower than poliplexes both in vitro and in vivo. After 24 hours of intravenous injection of lipoplexes, gene expression led us to specific transfection in the lung with the transferrin-protamine formulation, and in the liver in the case of the administration of asialofetuin-protamine complexes. The good transfection efficiency and high viability in vitro and in vivo indicates that lipoplexes could be an interesting alternative to viral vectors in the treatment of some diseases through gene therapy strategies.