The blood brain barrier (BBB) is a specialized endothelium that prevents the uptake of substances from the systemic circulation into the central nervous system. This barrier, while protecting the sensitive physiological environment of the brain, is also a major impediment in administering therapeutics that need to pass through the BBB. A drug delivery platform that could deliver therapeutic agents directly to the brain is needed, and could have wide ranging significance in a variety of psychiatric, oncology, infectious, and neurodegenerative diseases. Currently, there are no approved formulations that can effectively increase drug exposure to the brain, and this remains an unmet clinical need.
Investigators in the Nanotechnology Characterization Laboratory at the National Cancer Institute (NCI) have developed a selective polylysine succinylated (PLS) drug delivery platform, which can pass through the BBB by scavenger receptor A1 (SR-A1)- mediated transcytosis, and also target SR-A1 expressing cells, such as macrophages, monocytes, mast cells, and dendritic cells. This PLS polymer has an anionic backbone, containing pendant carboxylic acids that facilitate conjugation of therapeutic agent having a free alcohol moiety via hydrolysable ester bonds. Thus, the PLS platform has tremendous versatility in delivering a wide variety of therapeutic cargos to the brain. In addition to small molecules, other classes of therapeutic drugs that can be conjugated to the PLS polymer include nucleic acids and peptides. In addition to delivering therapeutic agents, this technology can also be used for imaging applications by conjugating imaging agents to the PLS polymer. This technology is a variant of the PLS drug delivery platform previously developed by the inventors (NIH Reference # E-097-2017).
Through in vivo mice fluorescent studies, the inventors have shown greater brain distribution with 10k and 25k PLS polymers in comparison to a larger, 62.5k polymer. This polymer platform has tremendous potential to increase drug delivery to the brain and lymphatic system, as well as stabilize metabolically labile drugs. It offers a novel therapeutic strategy for treating brain cancers and other neurological disorders. It also brings a novel imaging approach for diagnostic purposes.
The NCI seeks research co-development partners and/or licensees for this technology.