Brain Delivery of NAP with PEG-PLGA Nanoparticles Modified with Phage Display Peptides

A phage-displayed peptide TGN was used as a targeting motif to help the delivery of NAP-loaded nanoparticles across the blood-brain barrier (BBB), which sets an obstacle for brain delivery of NAP in vivo. Intracerebroventricular injection of A beta(1-40) into mice was used to construct in vivo model of Alzheimer's disease. The water maze task was performed to evaluate the effects of the NAP formulations on learning and memory deficits in mice. The neuroprotective effect was tested by detecting acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity and conducting histological assays. Intravenous administration of NAP-loaded TGN modified nanoparticles (TGN-NP/NAP) has shown better improvement in spatial learning than NAP solution and NAP-loaded nanoparticles in Morris water maze experiment. The crossing number of the mice with memory deficits recovered after treatment with TGN-NP/NAP in a dose dependent manner. Similar results were also observed in AChE and ChAT activity. No morphological damage and no detectable A beta plaques were found in mice hippocampus and cortex treated with TGN-NP/NAP. TGN modified nanoparticles could be a promising drug delivery system for peptide and protein drug such as NAP to enter the brain and play the therapeutic role.