Effective delivery of therapeutics into the brain is challenging, due to biological barriers including the blood-brain barrier (BBB), the perivascular space, cerebrospinal fluid, and the extracellular matrix. Drugs that can cross the BBB may be delivered intravenously; for drugs that cannot penetrate the BBB, intrathecal or local administration provide alternative delivery methods, but these are invasive. Other techniques exist to create temporary openings in the BBB for drug delivery or encapsulating drugs within inert polymer-based coatings to achieve effective transport. Despite extensive efforts to improve drug delivery across the BBB, ~98 percent of small molecules and nearly 100 percent of all biologic therapeutics are unable to shuttle across the BBB.
Dr. Rana Ghosh and his team have identified peptides that penetrate the blood-brain barrier, with delivery observed in both in vitro and in vivo models. BBB-penetrating peptides were identified by panning a phage display library against an established BBB model to identify peptides that were selectively enriched over several rounds of panning. Subsequent in vitro and in vivo studies indicate that this high-throughput screening technique successfully identified select peptides as promising carriers able to overcome multiple biological barriers of the brain and shuttle different-sized molecules, from small fluorophores to large macromolecules (e.g., nanoparticles), into the brain, realizing improved drug and gene delivery into the brain.
Dr. Ghosh is an Associate Professor of Molecular Pharmaceutics and Drug Delivery at The University of Texas at Austin, with primary research interests in biologically inspired, rational design of biomolecules (e.g., peptides, proteins) and the creation of nanoscale materials for the development of therapeutics in cancer and mucosal-associated diseases. He has published over twenty research papers and has been awarded numerous U.S. patents. The focus of his work has broad applicability in the integration of pharmaceutical sciences with biotechnology, biological engineering, and materials science.
https://pubmed.ncbi.nlm.nih.gov/38085066/