Functional Nanostructured Materials as Matrices for Controlled Release

Nanostructured drug delivery systems (DDS) have drawn great attention in these last years due to the improvement of the efficacy of therapeutic principle, by enhancing their biocompatibility, bioavailability and targeting. Particular interest was focused on the design and development of multifunctional architectures for the delivery of different therapeutics and diagnostic agents and their spatially and temporally controlled release. In this study we report the design, synthesis and characterization of two main categories of nanostructured functional materials for drug delivery: simple DDS based on inorganic and magnetic nanoparticles (MNPs) and more complex hybrid responsive platforms based on lipids and MNPs. Calcium Phosphate NPs decorated with oligonucleotide single and double strands as nanocarriers for gene delivery endowed of high biodegradability and biocompatibility, were synthesized and characterized by DLS and Atomic Force Microscopy. Moreover, magnetic core-shell hydrophobic and hydrophilic nanoparticles of magnetite (Au@Fe3O4) were prepared and characterized through DLS and SAXS. These MNPs, having suitable sizes to be incorporated in the lipid bilayers and in the aqueous core of liposomes (magnetoliposomes), were used as actuators for the magnetic triggered release of Carboxyfluorescein from the core of liposomes dispersed in biological fluids (serum 10% and 55% in protein concentration), in order to study the effects of the serum proteins on the release behavior. The design, preparation and characterization of another hybrid lipid/MNPs DDS, where hydrophobic Fe3O4 NPs are embedded in the bilayer of bicontinuous cubic lipid phase of Glyceryl Monooleate (GMO), either in bulk phase and in dispersed cubic lipid nanoparticles (magnetocubosomes), were performed. Furthermore, for the first time Fluorescence Correlation Spectroscopy was employed to investigate the magnetoliposomes’ ability to encapsulate simultaneously both hydrophilic and hydrophobic drugs and also to study their diffusion inside the bicontinuous cubic phase domains. Finally, with the same technique a magnetically triggered release of a hydrophilic model drug toward an aqueous environment from aqueous channels of both bulk cubic phase, doped with MNPs, and magnetoliposomes was monitored highlighting that a low-frequency alternating magnetic field (LF-AMF) can act as an external trigger to boost the release of a model drugs confined in the cubic phase.