Developing an effective drug delivery system for neurodegenerative diseases to bypass the CNS resistance to treatment

The blood-brain barrier (BBB) limits drug delivery to the central nervous system (CNS). There is a need for safe and effective drug delivery systems targeting the CNS. Our published results on short peptides from the (RW)n series show their ability to cross the BBB, making them potential candidates for treating neurodegenerative diseases; furthermore, they are non-toxic to mammalian cells. The goal is to study the molecular mechanism by which peptides from the (RW)n series cross the BBB, which will guide research and enhance drug delivery effectiveness to fully treat neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The mechanisms behind short peptides' translocation across the BBB and cell membranes are not fully understood due to limitations in detection and localization methods. To fill this knowledge gap, our main hypothesis aims to investigate whether short peptides of the (RW)n series can cross the BBB, as they contain a certain number of tryptophan (W) residues that enhance their detectability through fluorescence and electron microscopy. The presence of these W residues offers two advantages: it enables tracking the peptides and observing their location relative to the model membrane using biophysical techniques such as fluorescence imaging and AFM, and the unique properties of W residues drive the peptides toward the hydrophobic core of the lipid bilayer. The rationale for this research is that understanding the transport mechanism of these peptides could lead to the development of pharmacological agents capable of crossing the BBB for more effective treatment of chronic infections. Both conjugated and non-conjugated complexes of (RW)n peptides with selected drugs will be tested. This project is innovative because (a) it enhances our knowledge of how drugs and active pharmaceutical agents are transported across the BBB, and (b) it lays the foundation for developing therapeutic strategies that target the structure of the BBB.