The Design and Construction of Botulinum Toxin Drug Delivery Vehicles

This proposal describes strategies to develop a neural cell specific delivery vehicle system which utilizes the target specificity of the botulinum toxin family to provide a generic platform for the delivery of drugs to the neuronal cytosol. Using a multi-disciplinary approach, we will construct and evaluate a non-toxic form of botulinum neurotoxin (BoNT) for use as a neural cell specific delivery vehicle. In Phase I, we will set out to accomplish: 1) Construct of BoNT-derived delivery vehicles coupled to a reporter molecule. 2) Evaluate the delivery capabilities of the BoNT-derived vehicles. 3). Determine the minimal components of BoNT for successful drug delivery. In Phase II, we will: synthesize aminoquinoline derivatives that can be coupled to the delivery vehicle and increase the number of BoNT delivery vehicle delivery drug binding sites. The work proposed here is intended to lead to systems which will function as important pharmacological delivery systems in antitoxin therapy and possibly serve in targeting therapeutic agents to nerve terminals for a variety of disease states. BENEFITS: These drug delivery vehicles have potential as antitoxin therapeutics under battle field conditions. They also would benefit consumer food safety as well as create new applications in medical therapeutics for the treatment of various neurological disorders. The dual use applications of this technology are economically significant.