Brain delivery of biotinylated NGF bounded to an avidin-transferrin conjugate.

Recent study showed that transferrin receptors were concentrated on the plasma membrane of brain endothelia cells and mediated transcytosis of transferrin (Tf) through the blood-brain barrier (BBB). This property allows the transferrin to act as the brain drug transporter vector. The present investigation examined the pharmacokinetic behavior of nerve growth factor (NGF), which was conjugated to transferrin by the avidin/biotin technology, especially its brain-uptake efficiency. The area under the plasma concentration curve and the mean residence time were not significantly different for either bio-NGF or bio-NGF/AV-Tf. At the first hour after single intravenous injection, the BBB permeability surface area product of bio-NGF/AV-Tf was 0.77 microliter/min/g; it was about 8-fold higher than that of bio-NGF, and equal to that of AV-OX26. The delivery of bio-NGF/AV-Tf to brain was 0.075% of injected dose per gram brain, and it was 5-fold higher than that of bio-NGF, and 2-fold higher than that of AV-OX26. In summary, these studies demonstrated that the use of Tf as brain drug delivery vector was as effective in transporting biotinylated therapeutics as OX26, and avoided the disadvantages of its antigenicity.