Drug targeting to the brain

Area of Science:

• Neuroscience
• Pharmacology
• Biotechnology

Background:

• The blood-brain barrier (BBB) restricts the entry of therapeutics into the brain.
• Effective drug delivery to the brain is crucial for treating neurological disorders.

Purpose of the Study:

• To explore strategies for delivering therapeutics across the human blood-brain barrier (BBB).
• To utilize endogenous transporters and molecular Trojan horses for enhanced brain drug targeting.

Main Methods:

• Re-engineering pharmaceuticals to utilize specific endogenous transporters (e.g., insulin, transferrin) for receptor-mediated transport (RMT) across the BBB.
• Employing peptidomimetic monoclonal antibodies (MAb) as molecular Trojan horses to ferry large molecules across the BBB.
• Developing fusion proteins combining molecular Trojan horses with therapeutic agents (neurotrophins, antibodies) for targeted brain delivery.
• Utilizing Trojan horse liposome technology for brain targeting of non-viral gene medicines (plasmid DNA).

Main Results:

• Demonstrated that endogenous peptides and MAb can cross the BBB via RMT.
• Showcased the potential of MAb as Trojan horses for delivering large pharmaceuticals like proteins, RNA interference drugs, and gene medicines.
• Confirmed that engineered fusion proteins retain dual functionality: BBB receptor binding for transport and brain receptor binding for therapeutic effect.
• Validated Trojan horse liposome technology for delivering non-viral plasmid DNA across the BBB.

Conclusions:

• Molecular Trojan horse strategies, including fusion proteins and liposomes, enable targeted delivery of diverse large-molecule pharmaceuticals to the brain.
• This technology holds significant promise for treating brain disorders by overcoming the BBB challenge.
• Future applications include targeting virtually any large molecule pharmaceutical to the brain using these advanced delivery systems.