Screening on-chip fabricated nanoparticles for penetrating the blood–brain barrier

The inability of drugs to cross the blood-brain barrier (BBB) makes it difficult to treat diseases in the central nervous system. It is known that peptides with or without specific receptors on the BBB showed different or even controversial neuron targeting capability in different reports. So, it is necessary to clarify how these peptides work as targeting molecules in the central nervous system. Herein, we evaluate and compare the performance of 6 kinds of peptides with (T7, D-T7, and GSH) or without (TGN, CGN, and TAT) BBB-specific receptors by conjugating these peptides on lipids to serve as a shell to encapsulate a core of PLGA and lamotrigine to form nanoparticles for targeted epilepsy therapy. In vitro assay shows that the TAT-modified nanoparticles show the highest internalization efficacy in the BBB model cell line bEnd·3 cells and hippocampal neurons. By contrast, experiments in mice show that the D-T7-modified nanoparticles have the highest brain targeting and epilepsy therapeutic efficiency. Thus, our experiments uncover the different performances of the 6 peptides at different levels (in vitro and in vivo), which is insightful for developing novel delivery systems for treating diseases in the central nervous system.