RAPAMYCIN LOADED SOLID LIPID NANOPARTICLES: FORMULATION, CHARACTERIZATION AND INHIBITION OF mTORC1 ACTIVITY IN SH-SY5Y NEUROBLASTOMA CELLS.

Recently, rapamycin (rp) specific inhibition of the mTOR complex has led to succesful treatment of cognitive disorders in an AD mouse model. The design of rp loaded polysorbate 80-coated solid lipid nanoparticles (rp-P80-SLN) could be a useful strategy to target CNS disorders by limiting the rp immunosuppressive side effect. Rp-P80-SLN (10 and 20 % w/w) were prepared using Compritol® 888ATO and cold high-pressure and ultrasound assisted homogenization methods. The SLN were characterized by UV-vis, HPLC, DSC, XRD, DLS, zeta-potential, SEM and cryo-TEM, and tested in vitro using pulse and chase regimen on the SH-SY5Y neuroblastoma cell line. The SLN size was in the range 50-200 nm with 30-40% encapsulation efficiency and slightly negative surface charge. They were round shaped with homogeneous surface and a β’-polymorph inner structure. Size and content did not change significantly over 3 months incubation at 4°C. The rp-P80-SLN were uptaken efficiently over 4 hours incubation with SH-SY5Y cells. They resulted non-toxic in the 2-20 nM rp concentration range. SLN had prolonged effect compared to rp solution with a superior antiproliferative effect and inhibition of the mTORC1 complex. The rp-P80-SLN could be useful tools to treat neurodegenerative disorders. Their successful application should pass through the limitation of the strong immunosuppression affecting long-term rp administration.