Polymers that bind small and large molecules are of widespread importance across an array of areas, and critical to pharmaceutical, personal care, food, fragrance, agrochemical, drug delivery, and chemical sensing applications. The physical and chemical interactions between polymers and small/large molecules have a strong influence over the performance of a given system, dictating many crucial properties. For example, polymers aid shelf-life stability of oral drug and personal care formulations, dictate aggregation stability and bioavailability for biologic therapeutics, and control release of various active ingredients such as antimicrobial agents, therapeutics, antioxidants and stabilizers, fragrances, and flavors. In addition, polymers can serve as affinity agents for capture of contaminants and/or chemical sensing of unwanted species in water and food matrices.
The overarching goal of this project to understand the way molecular interactions dictate structure and function in polymer formulations with small and large molecular actives. Our lab aims to understand on the molecular-level the forces that dictate polymer-molecule association, binding affinity, and macromolecular/supramolecular assembly of these new materials into nano- and micro-architectures. The long-term goal is to enable rational design of tailorable, modular, and effective materials for a variety of molecule engineering applications, ranging from drug and protein delivery to chemical sensing of toxins in water and food. Our lab is highly collaborative with a number of groups across the UMN campus and corporate partners in this research space.
Featured Projects: Engineering Molecule–Polymer Interactions
Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, several approaches for designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs are highlighted. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.
Reference: J. M. Ting, W. Porter, J. Mecca, F. S. Bates, T. M. Reineke "Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery", Bioconjugate Chem. 2018, 29, 939–952.
Modifications to the aqueous solution self-assembly and thermoresponsive properties of poly(N-isopropylacrylamide) (PNIPAm) can be achieved by hydrophobic end-group functionalization and incorporation of hydrophilic N,N-dimethylacrylamide (DMA) repeat units. Although these variations have been studied separately in the past, the simultaneous effects of both modifications have not been investigated systematically. Several NIPAM- and DMA-based statistical, ABA triblock, and ABABA pentablock copolymers were synthesized using reversible addition–fragmentation chain transfer (RAFT) polymerization for this study. The results of this work demonstrate surprising and delicately balanced tradeoffs between short non-polar end groups and tailored hydrophobicity in the nanoscale self-assembly of PNIPAm based copolymers in water near the lower critical solution temperature.
Reference: M. L. Ohnsorg, J. M. Ting, S. D. Jones, S. Jung, F. S. Bates, T. M. Reineke "Tuning PNIPAm Self-Assembly and Thermoresponse: Roles of Hydrophobic End-Groups and Hydrophilic Comonomer", Polym. Chem. 2019, 10, 3469–3479.