Rapamycin-loaded polysorbate 80-coated PLGA nanoparticles: Optimization of formulation variables and in vitro anti-glioma assessment

Rapamycin is a promising anticancer agent, but because it has poor water solubility and low bioavailability its clinical use is limited. The aim of this study was to develop rapamycin-loaded poly(lactide-co-glycolide) nanoparticles coated or not with polysorbate 80 for drug delivery to glioma cells. Nanoparticles were prepared using the emulsification-diffusion method, formulated and optimized through Box-Behnken design, and characterized by DLS, SEM, and DSC. In vitro drug release and stability studies were also performed. The anti-glioma activity of the optimized nanoformulations was tested on C6 glioma cells by cytotoxicity assay and cytoskeletal integrity assessment. The respective values for the particle size, polydispersity index, zeta potential, and drug entrapment efficiency of the optimized uncoated and polysorbate 80-coated nanoparticles were 232 vs. 247 nm, 0.059 vs. 0.103, -16.69 vs. -11.76 mV, 43.7 vs. 28.51%. SEM and DSC analyses revealed that rapamycin was entrapped into spherical nanoparticles. These nanoparticles showed a biphasic drug release pattern and exhibited satisfactory storage stability for at least three months. Anti-glioma activity studies demonstrated that the polysorbate 80-coated nanoparticles were more effective than the uncoated ones and the free rapamycin. These findings suggest that these nanoformulations could be useful in glioma chemotherapy.