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

Neurodegenerative disorders, such as Alzheimer, Parkinson or lysosomal storage diseases belong to most delibitating diseases of affluence which continuously remain without any efficient, low-cost remedy. Much effort has been paid for inventing effective brain-targeted drug composites to sufficiently overcome the blood-brain barrier, that constitutes a natural system strictly regulating the transport into the central neural system from the blood or cerebrospinal fluid. At the same time, specific inhibition by rapamycin of the mTOR complex, i.e. mammalian target of rapamycin displaying Ser/Thr kinase activity, responsible for autophagy, metabolism and cell proliferation, has been recently demonstrated to repair the cognitative behavior in a Alzheimer mouse model. Hereof, design of well-defined solid lipid nanoparticles carrying rapamycin becomes a powerful strategy to cross the BBB and treat the central nervous system-localized lesions. Rapamycin-loaded SLN (10 and 20 % w/w), based on cetyl palmitate, Compritol® ATO888 and Geleol® as matrixes and stabilized with 1% polysorbate 80, were prepared using a cold high-pressure homogenization, solvent evaporation and dialysis protocol. Drug content and thermal stability of the nanoformulations were established exploiting DSC, UV-NIR and XRD, whereas DLS, zeta-potential, particle tracking and SEM measurements revealed their colloidal size distribution (50, 100, 200 nm). These favorable properties made the rapamycin-loaded SLN useful for in vitro treatment of a SH-SY5Y neuroblastoma cell line, i.e. an in vitro model for neurodegenerative diseases. Long-term studies of MTT toxicity and mTOR activity provided a promising evidence for controlled rapamycin release from lipid matrixes in cytosol, what confirms a potential biomedical application of the nanoformulations.