Abstract:

Brain-derived neurotrophic factor (BDNF) plays an important role in the repair of central nervous system injury, but cannot directly traverse
the blood-brain barrier. Liposomes are a new type of non-viral vector, able to carry macromolecules across the blood-brain barrier
and into the brain. Here, we investigate whether BDNF could be transported across the blood-brain barrier by tail-vein injection of liposomes
conjugated to transferrin (Tf) and polyethylene glycol (PEG), and carrying BDNF modified with cytomegalovirus promoter (pCMV)
or glial fibrillary acidic protein promoter (pGFAP) (Tf-pCMV-BDNF-PEG and Tf-pGFAP-BDNF-PEG, respectively). Both liposomes were
able to traverse the blood-brain barrier, and BDNF was mainly expressed in the cerebral cortex. BDNF expression in the cerebral cortex was
higher in the Tf-pGFAP-BDNF-PEG group than in the Tf-pCMV-BDNF-PEG group. This study demonstrates the successful construction
of a non-virus targeted liposome, Tf-pGFAP-BDNF-PEG, which crosses the blood-brain barrier and is distributed in the cerebral cortex.
Our work provides an experimental basis for BDNF-related targeted drug delivery in the brain.

Key words: nerve regeneration, brain injury, brain-derived neurotrophic factor, liposomes, targeting, vector, transfection, hippocampus, cortex, encapsulation efficiency, blood-brain barrier, transferrin, glial fibrillary acidic protein, polyethylene glycol, neural regeneration