Traversing the blood brain barrier with endocytosed monocytes

Crossing the blood brain barrier (BBB) is difficult, because the tight peripheral endothelia only allows molecules that are both lipid soluble and smaller than 400 daltons. Use this converter to find out how tiny of a molecular mass that is, and you will begin to recognize the difficulties. Microencapsulating neuropharmaceuticals in immunoliposomes that are already directed for the brain is considered a promising step in overcoming this difficulty.

Afergan et al recently reported on the use of two phagocytic cells of the immune system, monocytes and neutrophils, as transporters of serotonin to the brain. Serotonin, which cannot naturally penetrate the BBB, was first encapsulated in a negatively charged liposome. The liposomes endocytosed in both phagotyic cells, but at a higher uptake rate by the monocytes. Via flourescent microscopy the researchers could detect that they passed the BBB intact in rabbits, and were subsequently secreted by the phagocytic cell.

Four hours after administering the serotonin via liposomes and simply in solution, the concentration of serotonin in the brain was 0.138% +/- 0.34 for the serotonin liposomes and 0.068% +/- 0.02 for the group with serotonin in solution, which was a significant increase. Despite the improvement, the authors note that the technique is not yet clinically relevant because it was simply not potent enough. If the process could somehow be iterated upon and improved, it is possible that this method could see some daylight in the future.


Afergan E, Epstein H, Dahan R, Koroukhov N, Rohekar K, Danenber HD, Golomb G. 2008 Delivery of serotonin to the brain by monocytes following phagocytosis of liposoms. Journal of Controlled Release 132:84-90. doi:10.1016/j.jconrel.2008.08.017.

Cornford EM, Hyman S. 1999 Blood–brain barrier permeability to small and large molecule. Advanced Drug Delivery Reviews 132:145-163. doi:10.1016/S0169-409X(98)00082-9.