Research

Polymers and Lipids for Nucleic Acid Delivery

We design polymeric and lipid-like vehicles that package and deliver nucleic acids, including pDNA, mRNA, ASOs, siRNA, and gene editing systems such as CRISPR ribonucleoproteins and base editors, into cells, tissues, and animals. Work here starts at the monomer: group members synthesize novel cationic, carbohydrate, and alkaloid-derived monomers (trehalose, glucose, GalNAc, quinine and other cinchona scaffolds), then polymerize them by controlled radical and ring-opening methods, most often RAFT, to build statistical copolymers, diblock and triblock micelles, bottlebrushes, and degradable polycarbonates with defined molar mass, dispersity, and architecture. Vehicles are characterized by NMR, SEC-MALS, DLS, cryo-TEM, SAXS/SANS, ITC, and Raman and fluorescence spectroscopy to connect chemical structure to assembly, payload binding, and unpackaging. We have shown that amine type governs mRNA binding and lung-selective expression in vivo, and that amphiphile identity and micelle morphology redirect delivery between lung and spleen while lowering inflammatory response. Combinatorial library synthesis, parallelized screening, and machine learning let us extract design rules rather than one-off hits, with disease targets spanning primary immunodeficiency, epidermolysis bullosa, HIV reservoirs, and ovarian cancer.

Small Molecule Drug Delivery

We develop polymer excipients that solubilize and stabilize poorly water-soluble active pharmaceutical ingredients, largely as spray-dried amorphous solid dispersions (ASDs) for oral administration. We treat the drug/polymer pair as a designable noncovalent interaction problem, and synthesis is central to it: group members prepare excipient libraries by RAFT and grafting-through approaches with systematic control over comonomer composition, ionizable and hydrogen-bonding group density, molar mass, end-group chemistry, and architecture, from statistical and block copolymers to bottlebrushes with tunable side-chain and backbone lengths. Formulations are then interrogated by NMR and SEC, DSC and TGA, synchrotron X-ray diffraction, cryo-TEM and scattering, ITC, rheology, and dissolution and permeation assays. Recent results establish that carboxylic acid content in bottlebrush poly(acrylic acid) scales linearly with solubility maintenance through electrostatic interaction, and that nanodroplet morphology on dissolution dictates performance. The same framework extends to protein stabilization, surfactants, and personal care actives with our industry partners.

Sustainable Polymers and Formulation

We build monomers, polymers, and formulation ingredients from renewable feedstocks such as cellulose, levoglucosan, sugars, terpenes, isosorbide, and seed oils, using green chemistry aimed at a circular materials economy. Organic and macromolecular synthesis is central to this work. Group members design and scale biomass-derived monomers, screen biocompatible and recyclable catalysts such as metal triflates for cationic ring-opening polymerization, and apply photoinitiated thiol–ene and other click chemistries for polymerization and post-polymerization modification. A major current thrust is homogeneous cellulose modification in ionic liquid media, where we have developed catalyst-free etherification that reaches high, tunable degrees of substitution in minutes and thiol–ene routes giving precise control over water-soluble cellulosics for rheology modification, controlled release, and home and personal care formulation. We characterize these materials from reaction kinetics through NMR, mass spectrometry, SEC, thermal analysis, mechanical testing, X-ray scattering, and rheology, extending the work to degradable and recyclable networks and adhesives, self-assembling glycolipids, and polysaccharide hydrogels and microcarriers for cell therapy manufacturing.

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