Development of silibinin-loaded nanostructured lipid carriers for Alzheimer's disease induced by amyloid beta in Wistar rats

Objective. The purpose of this study is to develop, optimize, and evaluate the in vivo effectiveness of orally administered silibinin-loaded nanostructured lipid carriers (SB-NLCs) in amyloid β-induced Alzheimer's disease in Wistar rats. Methods. The emulsification-solvent evaporation method was used for preparing the NLCs, using stearic acid, triacetin, and Cremophor® RH40. The statistical optimization of SB-NLCs was done using the Box–Behnken design (BBD). Then, the following parameters were evaluated: zeta potential, average size, in vitro drug release, and drug entrapment efficiency. Physicochemical properties of the optimized SB-NLCs were determined by FTIR, DSC, and P-XRD. The behavioral (OFT, NOR, MWM), histological (H&E, Congo Red), and biochemical (TAC, MDA, GSH) tests were conducted on 48 male Wistar rats. Results. The findings showed that the mean particle size, zeta potential and entrapment efficiency of optimized SB-NLCs were 194.71 ± 14.06 nm, −12.46 ± 0.25 mV, and 72.13% ± 1.41, respectively. XRD and DSC studies confirmed a reduction in the crystallinity of SB which occurred due to its embedment in the nanostructured lipid. The FTIR results indicated the lack of existence of any chemical interaction between the carrier components and the drug. Drug release in the external environment was slow and steady. Drug-containing nanoparticles showed good stability during three months of storage at 4 °C. The behavioral test of OFT showed no significant change between groups. The group treated with SB-NLCs showed a markedly higher discrimination rate compared to the Aβ group (p < 0.001). The time of the SB-NLC treated group in the target area was considerably more than the time of the SB and Aβ groups, respectively (p < 0.01, p < 0.001), in the MWM test. Histological and biochemical analysis revealed better results in the SB-NLC group as against the SB group. Conclusion. SB-NLCs can be considered as a promising formulation for the proper treatment of Alzheimer's disease in the oral drug delivery system.