Enzyme Targetted Therapeutics

BACKGROUND Enzymes, especially proteases play essential roles in disease specific processes and are valuable targets for therapeutic intervention. A number of methods of targeting enzymes have been used to date. These include specific enzyme inhibitors and polymeric carriers which disintegrate to release pro-drug in response to disease related enzymes. Dr. Rein Ulijn of the School of Materials at the University of Manchester has developed bio-responsive hydrogels that selectively expand on contact with specific enzymes releasing drug entrapped within the hydrogel at the precise site where it is needed. THE TECHNOLOGY The drug to be delivered is physically entrapped inside shrunken hydrogel beads with attached zwitterionic (neutral) peptide linkers which have the dual role of acting as both enzyme sensors and actuators of drug release. When the target enzyme comes into contact it cleaves the peptide linker, removing a charged fragment and causing the hydrogel to become oppositely charged (see diagram). This process causes the hydrogel to swell (through electrostatic repulsion) releasing its drug load at the site of the target enzyme [right-hand images show fluorescent-labelled payload trapped (lhs) and after release (rhs)). This approach represents a significant advance over enzyme targeted drug delivery methods used to date. The technology enables drug-delivery on demand only in the presence of disease-related enzymes of choice with kinetics that may be tuned by design of the polymer particles (e.g. burst release or sustained release profiles are feasible). The method is particularly useful for delivery of hard-to-deliver biomacromolecules such as proteins. KEY BENEFITS
• Bio-compatible
• Hydrogels are selective - only respond to a single enzyme
• Tailored and facile application-specific hydrogel design
• Drugs to be delivered do not need to be chemically modified
• Hydrogels ideal for wet biological environments
• Low-cost materials
• Drug release is triggered by enzyme action, but pharmacokinetics are determined by the polymer composition APPLICATIONS
• Enzyme targeted drug-delivery
• Cancer treatment
• Localised ‘on-demand’ delivery of anti-inflammatory agents INTELLECTUAL PROPERTY An international patent has been filed. OPPORTUNITY The technology is currently at an early-stage where ‘proof-of-concept’ has been demonstrated. A collaborative partner or agent is sought to assist the development of candidate drugs.

Type of Offer: Licensing

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