Defining Structure-Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra-Stable Biopharmaceuticals.

Biopharmaceuticals are the fastest-growing class of drugs in the healthcare industry, but their global reach is severely limited by their propensity for rapid aggregation. Currently, surfactant excipients such as polysorbates and poloxamers are used to prevent protein aggregation, which significantly extends shelf-life. Unfortunately, these excipients are themselves unstable, oxidizing rapidly into 100s of distinct compounds, some of which cause severe adverse events in patients.

Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.

Single-particle cryo-EM is widely used to determine enzyme-nucleosome complex structures. However, cryo-EM sample preparation remains challenging and inconsistent due to complex denaturation at the air-water interface (AWI). To address this issue, we developed graphene-oxide-coated EM grids functionalized with either single-stranded DNA (ssDNA) or thiol-poly(acrylic acid-co-styrene) (TAASTY) co-polymer.

Extreme Extensibility in Physically Cross-Linked Nanocomposite Hydrogels Leveraging Dynamic Polymer-Nanoparticle Interactions.

Designing yield stress fluids to exhibit desired functional properties is an integral challenge in many applications such as 3D printing, drilling, food formulation, fiber spinning, adhesives, and injectable biomaterials. Extensibility in particular has been found to be a highly beneficial characteristic for materials in these applications; however, few highly extensible, high water content materials have been reported to date. Herein we engineer a class of high water content nanocomposite hydrogel materials leveraging multivalent, noncovalent, polymer-nanoparticle (PNP) interactions between modified cellulose polymers and biodegradable nanoparticles.

Affinity-Directed Dynamics of Host-Guest Motifs for Pharmacokinetic Modulation Supramolecular PEGylation.

Proteins are an impactful class of therapeutics but can exhibit suboptimal therapeutic performance, arising from poor control over the timescale of clearance. Covalent PEGylation is one established strategy to extend circulation time but often at the cost of reduced activity and increased immunogenicity. Supramolecular PEGylation may afford similar benefits without necessitating that the protein be permanently modified with a polymer.

Engineering Insulin Cold Chain Resilience to Improve Global Access.

There are 150 million people with diabetes worldwide who require insulin replacement therapy, and the prevalence of diabetes is rising the fastest in middle- and low-income countries. The current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple "drop-in" amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics, and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks.