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).
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