(4aq) Tailoring Ionic Block Copolymer Structure and Function for Therapeutics Delivery and Energy Applications

Green, M. D., University of Delaware

The tunable chemical composition, thermomechanical properties, and nanoscale morphologies of block copolymers enable access to myriad applications, including energy storage and harvesting devices as well as drug and gene delivery vehicles.  My graduate research (with Prof. Timothy Long, Virginia Tech) focused on using controlled radical polymerization techniques to prepare designer triblock copolymers for electromechanical transducers.  Electromechanical transducers have potential applications in energy harvesting devices, biomimetic materials, and sensors.  However, the design of polymeric systems that maximize both ion transport and mechanical strength has been challenging, which has limited performance and marketability.  Therefore, I developed systematic structure-property relationships for imidazole-containing homopolymers and block copolymers, which enabled the design of ionomeric membranes that optimized ionic conductivity and storage modulus.  Specifically, I investigated the influence of (i) charge placement and density in the central and outer blocks; (ii) thermomechanical properties; (iii) ionic liquid incorporation; and (iv) chemical composition of the cation and anion on the properties of imidazole-containing polymers.  Ultimately, optimization of the ion content and thermomechanical properties in a triblock copolymer led to my preparation of the first successful cationic electromechanical transducer.

     My postdoctoral research (with Prof. Thomas Epps, III and Prof. Millicent Sullivan, University of Delaware) focuses on solution assemblies of diblock copolymers for drug and gene delivery.  Amphiphilic block copolymers form solution assemblies of a variety of structures based on the molecular weight and volume fraction of each component; these structures include spherical micelles, cylindrical micelles, and vesicles, which can be used to prepare drug delivery vehicles.  Specifically, we are interested in understanding the solution assembly of drug-loaded micelles and the assembly of light-activated nucleic acid delivery structures.  Our first set of studies is addressing the influence of the targeting ligand location on the solution assembly, cellular internalization efficiency, and in vivocirculation time; we have also analyzed the efficiency of hydrophobic drug encapsulation and delivery.  The novel series of amphiphilic block copolymers studied herein present a methodology for decoupling prolonged circulation and targeted therapeutic delivery, which could prove pivotal for effective drug delivery strategies.  Second, a series of light-activated diblock copolymers for gene delivery were prepared.  These block copolymers contain a non-fouling poly(ethylene oxide) block and a cationic block containing pendant photoactive nitrobenzyl functional groups.  The cationic block enables the condensation of anionic nucleic acids, and undergoes photocleavage upon irradiation with light.  This unique release mechanism enables controlled, externally stimulated delivery of nucleic acids, which presents exciting opportunities for gene delivery.

     The research directions of the program I plan to develop will explore bulk and solution assemblies of novel, ionic block copolymers for drug or gene delivery and energy applications.  This draws upon my graduate experience with polymerizable ionic liquids and incorporation of ionic liquids into membranes, while also utilizing my postdoctoral experience characterizing novel assemblies for drug and gene delivery.  Gaining inspiration from ionic liquids, I will design and prepare novel, ionic block copolymers with tunable chemical structures, thermomechanical properties, and targeted morphologies for energy storage devices.  Additionally, I will develop ionic block copolymers with tailored solution properties to optimize their performance as therapeutic delivery vehicles.  Ionic block copolymers present exciting opportunities for energy and therapeutic delivery applications, and developing novel structures with optimized performance will help revolutionize their utility and availability.