Abstract: | Lipid liquid crystalline nanoparticles can find application as nanocarriers in several
fields of the daily life but, very likely, the pharmaceutical arena is the most relevant.
Indeed, several problems encountered in drugs administration (e.g. critical sideeffects
from antitumor drugs) require alternative, less invasive, but simultaneously
efficient therapeutic routes to be explored. Novel fields of personalized
nanomedicine are developing in this direction. One of the most interesting is
theranostic, which calls for the design of platforms capable of combining therapeutic
and diagnostic functionalities.
In this optic, we explored the potential of monoolein-based cubosomes and
hexosomes as nanocarriers for theranostic purposes. Our work focussed on the
design of lipid nanoparticles able to deliver antineoplastic drugs and imaging probes
for fluorescent optical in vitro and in vivo imaging. We developed cubosome
formulations loaded with antineoplastic drugs and useful for the fluorescence
imaging of cells. Such formulations were also actively targeted to cancer cells and
coupled with a NIR-emitting fluorophore, which was the promise for in vivo
applications. We also investigated hexosomes with encouraging results
encapsulating in their lipid matrix a BODIPY derivative with solvatochromic
properties, helpful for the understanding of the dye localization.
Importantly, we reported (manuscript submitted) the first proof-of-principle for in
vivo fluorescence optical imaging application using monoolein-based cubosomes in
a healthy mouse animal model.
Finally, since relatively little is known about the interaction of cubosomes with
biological systems, their effects on lipid droplets, mitochondria and lipid profile of
HeLa cells were deeply studied.
This thesis is divided in two main parts. The introduction section reports on the
essential background of the research field, and it is followed by the publications
(published or submitted) resulting from these three years of work. |