Magnetoliposomes : effect of nanoparticles spatial distribution

Abstract

This thesis is focused on the design of nanocarries based on iron oxide nanoparticles and liposomes, that can be loaded with drugs for improving their targeting and efficiency. The combination of these two components represents a unique opportunity for achieving multiple therapeutic objectives. First of all it was studied the preparation and characterization of uniform iron oxide nanoparticles obtained by microwave assisted synthesis and compared them to those obtained by coprecipitation and thermal decomposition techniques, achieving core sizes from 8 to 15 nm (chapter 4.1). Selected samples were encapsulated in liposomes resulting in different spatial distributions: attached to the liposome surface, inside the lipid bilayer or inside the aqueous volume. Structural and magnetic characterization were also performed (chapter 4.2). The effect of the aggregation processes on magnetic properties have been analyzed in systems with different spatial distributions of the nanoparticles, as free nanoparticles, magnetoliposomes and cells incubated with nanoparticles (chapter 4.3). Finally, nanoparticles and magnetoliposomes are evaluated in-vitro to verify its limits of cytotoxicity in cells and then assessed as negative contrast agents for diagnosis with magnetic resonance imaging, for magnetic hyperthermia treatment and as carriers for doxorubicin, with controlled release by an applied alternate magnetic eld in different cell lines (chapter 4.4).

Esta tesis se centra en el dise~no de nanoestructuras basado en nanopart culas de oxido de hierro y liposomas. Pueden transportar medicamentos mejorando su localizaci on y e ciencia. La combinaci on de estos dos componentes representa una oportunidad unica para lograr m ultiples objetivos terap euticos. En primer lugar, se estudi o la preparaci on y caracterizaci on de nanopart culas uniformes de oxido de hierro obtenidas atrav es de s ntesis por microondas y se compararon con las obtenidas mediante t ecnicas de coprecipitaci on y descomposici on t ermica, logrando tama~nos de n ucleo de 8 a 15 nm (cap. 4.1). Muestras seleccionadas se encapsularon en liposomas que dieron lugar a diferentes distribuciones espaciales de las nanoparticulas: unidas a la super cie del liposoma, dentro de la bicapa lip dica o dentro del volumen acuoso. Tambi en se realiz o la caracterizaci on estructural y magn etica (cap. 4.2). El efecto de los procesos de agregaci on en las propiedades magn eticas se ha analizado en sistemas con diferentes distribuciones espaciales de las part culas, como part culas libres, magnetoliposomas y c elulas incubadas con part culas (cap. 4.3). Finalmente, se eval uan las part culas y los magnetoliposomas in-vitro para veri car sus l mites de citotoxicidad en las c elulas y se analiza su posible aplicaci on como agentes de contraste negativo para el diagn ostico con im agenes de resonancia magn etica, para el tratamiento de hipertermia magn etica y como portadores de doxorubicina, con liberaci on controlada por un campo magn etico alterno aplicado en diferentes l neas celulares (cap. 4.4).