Solid Lipid Nanoparticles Enhance Protective Effect of Rutin against STZ-Induced Neurotoxicity in PC12 Cells through Autophagy Suppression

Abstract

Rutin (Rut) has been identified as a neuroprotective compound with displayed beneficial effects in Alzheimer’s disease. However, low bioavailability and solubility are the major concerns pertaining to the use of Rut. Aberrant function of autophagy has been found as a well-established participant in the pathogenesis of neuronal degeneration. In the present study, Rut and Rut-loaded solid lipid nanoparticles (Rut-SLNs) were used to protect rat PC12 cells against streptozotocin- (STZ-) induced neurotoxicity. Rut-SLNs were fabricated by a solvent evaporation-ultrasonic method. Depending on the experimental patterns including pretreatment, cotreatment, and posttreatment, PC12 cells were exposed to STZ and desired doses of the SLNs, Rut, and Rut-SLNs. The viability of the cells, the mitochondrial membrane potential (MMP), and the expression of miR-21, miR-22, Akt, ATG5, Beclin1, and LC3 were evaluated by using MTT assay, rhodamine 123 fluorescent dye, and qRT-PCR, respectively. SLN and Rut-SLNs possess the smooth surface with an average size of 117.2 and 176.9 nm, respectively, with a negative zeta potential. The encapsulation efficiency and loading capacity of Rut in SLNs were 90.32% and 49.1%, respectively. The nanoformulation revealed a sustained drug release in vitro up to 72 h and followed Higuchi kinetics. Rut-SLNs displayed a neuroprotective effect by augmenting the viability of PC12 cells and increasing MMP. In addition, Rut-SLNs suppressed autophagy which was stimulated by STZ whereas, the free Rut demonstrated lower effect. Taken together, these results clearly indicated that Rut-SLNs could be a good candidate for the prevention of neurodegenerative diseases.