PHYSICOCHEMICAL CHARACTERIZATION OF RAPAMYCIN-LOADED SOLID LIPID NANOPARTICLES FOR BRAIN TARGETING

Brain disorders such as Alzheimer’s and lysosomal storage diseases belong to the most debilitating and progressive lesions of affluence, which still remain without an effective remedy. Due to the presence of the blood-brain barrier (BBB), i.e tight cell-to-cell connections in brain capillary walls, the transport of pharmaceuticals to the central nervous system is strictly regulated and at times forbidden. One of the most crucial protein complexes, that regulates vital processes within signal transduction, proliferation and autophagy pathways in the brain cells, is the mammalian target of rapamycin complex (mTOR). Specific targeting of the mTOR by rapamycin in-feed administration has been recently demonstrated to repair the cognitative behavior in the Alzheimer’s mice model. In light of an average size below 100 nm and lipophilic properties, P80-stabilized solid lipid nanoparticles (SLNs) have become a powerful, non-invasive strategy to overcome the BBB and release the drug directly into the brain tissue. We present a characterization of rapamycin loaded SLNs prepared using O/W emulsion - high-pressure homogenization technique and analyzed by means of Raman, UV-NIR and photon correlation spectroscopy. The effectiveness of the therapeutic application of SLN formulations will be validated in vitro on HEK293 and SH-SY5Y neuroblastoma cells and in vivo in normal and transgenic mice models.