Efficient brain drug delivery has been a challenge in the treatment of Alzheimer's Disease and other brain disorders as blood-brain barrier (BBB) impedes most drugs to reach brain. To overcome this obstacle, we developed a novel TGN decorated erythrocyte membrane-coated poly (lactic-co-glycolic acid) nanoparticle (TRNNs). The nanoparticle significantly boosted the penetration (7.3 times) in a U-118MG and HCMEC/D3 cell co-culture BBB model in vitro. Living image was performed to assess the TRNNs distribution in vivo. The fluorescence intensity in the isolated brain of TRDNs-treated mice was about 8 times that of the DNs-treated. In the novel object recognition test, the mice after administration of TRDNs showed higher recognition index (0.414 ± 0.016) than the model group (0.275 ± 0.019). A significant increase in the number of dendritic spines from TRNNs administrated mice hippocampi neurons was observed after Golgi stain. This improvement of neurons was also confirmed by the significant high expression of PSD95 protein level in hippocampi. We measured the OD values of Aβ25-35 induced PC12 cells that pre-treatment with different nanoparticles and concluded that TRNNs had a robust neuroprotection effect. Above all, functional biomimetic nanoparticles could increase the accumulation of naringenin into brain, thereby enable the drug to exert greater therapeutic effects.
Keywords: Alzheimer’s disease; Naringenin; blood-brain barrier; brain-targeted peptide; nano drug delivery system.