Therapeutic Delivery to the Brain via the Lymphatic Vasculature.

Targeted delivery of therapeutics to disease sites has been one of the biggest challenges in medicine, as it determines the treatment efficacy of virtually all chemical and biological drugs. Furthermore, it is particularly difficult to achieve for diseases in the brain because of an additional barrier compared to other organs, the blood-brain barrier (BBB). Here, we report a new mechanism for drug delivery to the brain, nanoparticle-mediated transport through the newly discovered brain lymphatic vasculatures, bypassing the BBB and other issues associated with conventional intravenous (i.v.) administration. Using indocyanine green (ICG)-loaded PLGA nanoparticles as a model, we show that drug uptake in the brain by subcutaneous (s.c.) injection at the neck near a local lymph node is 44-fold higher than the i.v. route, resulting in effective treatment of glioblastoma in mice by photodynamic therapy. These findings will open a new paradigm for the treatment of a variety of diseases in the brain.