(14a) Custom-Built Polymers Promote Stabilization, Delivery, and Bioavailability in Precision Drug Formulation Strategies | AIChE

(14a) Custom-Built Polymers Promote Stabilization, Delivery, and Bioavailability in Precision Drug Formulation Strategies


Ting, J. M. - Presenter, University of Chicago
Bates, F. S., University of Minnesota
Reineke, T. M., University of Minnesota
Tirrell, M. V., University of Chicago
Polymer excipients are inert but crucial ingredients in countless medicines to treat chronic, infectious, and inheritable diseases across the biomedical landscape. These enhancers serve numerous roles, such as the encapsulation of therapeutic cargos, stabilization for prolonged shelf life, protection against toxic side-effects, and control over spatiotemporal release. As early pipeline small molecule drugs and biopharmaceuticals with clinically intractable physiochemical attributes defy conventional controlled delivery strategies, renewed attention to excipients as designer biomaterials can reposition compounds with poor bioperformance to more successful and low-cost formulations. Here, I will describe a general high-throughput synthesis/screening campaign to rapidly explore the physical and chemical state spaces of multicomponent copolymers. As an example, combinatorial libraries comprising over 60 controlled polymers were constructed in three parallel runs to solubilize antiseizure and antiandrogen drugs in solid dispersions for oral drug administration. Narrow windows in chemical composition demonstrated drug supersaturation maintenance at an order of magnitude above equilibrium levels under nonsink in vitro dissolution conditions, supported by solution-state NOESY and DOSY NMR characterization. When administered to rat models, a 23-fold increase in the area-under-the-curve over the neat drug was observed, alongside superior bioavailability metrics over the use of commercial excipients. This integrated approach of combining core principles in engineering, chemistry, and biology illustrates the practical utility and broad potential of tunable polymer excipients toward the precision drug formulation of challenging therapeutic agents. I will conclude with ongoing efforts to adopt this paradigm toward the advancement of customized polyelectrolyte excipients. Advanced synchrotron scattering experiments provide insight on the encapsulation, size, and shape of designer nanocomplexes with peptides, nucleic acids, and proteins. This work can provide the foundation for nonviral delivery of CRISPR/Cas9 components in emerging gene editing frontiers.