Controlled Release of Ursodeoxycholic Acid from Pullulan Acetate Nanoparticles to Modulate Glutamate-Induced Excitotoxicity in PC-12 Cells

Abstract

The neuroprotective effects of the ursodeoxycholic acid- (UDCA-) loaded pullulan acetate (PA) (UDCA-PA) nanospheres stabilized by poly(vinyl alcohol) (PVA) were identified by in vitro study. The UDCA-PA nanospheres were constructed by nanoemulsion process. The UDCA-PA nanospheres were analyzed using Fourier transform-infrared spectroscopy (FT-IR) and transmission electron microscopy (TEM). Then, the UDCA-PA nanospheres were used to treat PC-12 neuronal cells, which were formerly triggered by glutamate-induced excitotoxicity. As a result, the cells treated with the UDCA-PA nanospheres showed higher survival rate against glutamate-induced excitotoxicity. Furthermore, the UDCA-PA nanospheres decreased immunoreactivity of Annexin V, a membrane marker for apoptotic cells, in PC-12 with glutamate-induced injury. Particularly, the UDCA-PA nanospheres decreased the level of apoptosis-related proteins such as caspase-3. Taken together, the UDCA-PA nanospheres increased neuroprotective effects against glutamate-induced neuronal damage via inhibition of apoptosis at low concentration.