Responsive Drug-Polymer Conjugate

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This award by the Biomaterials program in the Division of Materials Research to University of Illinois is to develop a new generation of polymer-drug conjugates that afford precise control over polymer-drug compositions, structure, drug loading and release. Conventional polymer-drug conjugates share the common feature such as a pre-synthesized water-soluble polymer with drug molecules being covalently conjugated to the pendant, conjugation-amenable groups via cleavage linkers. One key drawback of this design of polymer-drug conjugate is the lack of control of the chemical structure and composition, especially the control over pendant groups used for drug conjugation. The resulting material is essentially a mixture of numerous structure- and composition-distinct polymer-drug conjugates that each has its own therapeutic profile, clearance rate, distribution property, tissue penetration efficiency, etc. The proposed new generation of polymer-drug conjugates (chain-shattering polymeric therapeutic) would result in precise control over polymer-drug compositions, structure, drug loading and release. This system is basically an "AB" type of block copolymer, and the resulting nanoparticles are designed to be stable in aqueous solution because of the urethane and carbonate backbone structure. However, once a specific trigger is applied and the protecting groups of trigger-responsive domain "A" are removed, the backbone structure of chain-shattering polymeric therapeutic system becomes instantly unstable and quickly shatters to monomeric fragments resulting in drug release. The technological broader impact of the proposed system could be the development of well controlled drug-delivery materials that allow trigger-responsive and precise control over drug release both in vitro and in vivo. This system also would have the property similar as drug encapsulated systems that drug in its original form can be instantly released and exhibit therapeutic effects. Students working on this project would be trained in multidisciplinary areas such as organic synthesis, carry out controlled polymerization, preparation of polymer-drug conjugates and cell culture. The materials research will be widely disseminated with different outreach activities at the campus.Widely used present polymer based drug delivery systems share common features such as pre-synthesized water-soluble polymer with drug molecules being attached to pendant and conjugation-amenable groups via cleavage linkers. With this current system, it is difficult to overcome the drug being prematurely released from delivery systems prior to reaching their targets. To overcome some of these drawbacks, this research project will focus the development of drug conjugated systems (polymeric pro-drugs) with ease of handling and processability with no premature drug release. This system called chain-shattering polymeric therapeutics, in addition, would have the property similar to drug encapsulated systems with the drug in its original form that can be instantly be released for instant therapeutic effects. When the trigger is applied after the drug delivery materials arrive at the target or diseased tissue, the time, site and amount of drug released can be precisely controlled, which makes it possible to develop a personalized nanomedicine protocol. Students working on this research will be trained in the different aspects of materials research with respect to polymer based drug delivery system. The proposed research will be incorporated into outreach activities focusing underrepresented students at different levels from undergraduate to K-12. Other proposed outreach activities at University of Illinois include Discover Engineering Summer Camp programs and Engineering Open-House Program.