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.

Macromolecular Cargo Encapsulation via In Vitro Assembly of Two-Component Protein Nanoparticles.

Self-assembling protein nanoparticles are a promising class of materials for targeted drug delivery. Here, the use of a computationally designed, two-component, icosahedral protein nanoparticle is reported to encapsulate multiple macromolecular cargoes via simple and controlled self-assembly in vitro. Single-stranded RNA molecules between 200 and 2500 nucleotides in length are encapsulated and protected from enzymatic degradation for up to a month with length-dependent decay rates.

Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance.

Sustained Delivery of GLP-1 Receptor Agonists from Injectable Biomimetic Hydrogels Improves Treatment of Diabetes.

Unlabelled: Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L-cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. GLP-1 in itself is rapidly degraded, but long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central in the treatment of T2D because of the beneficial effects extending also beyond glucose control. Currently, these therapeutics must be injected either daily or weekly or taken daily orally, leaving room for technological innovations that enable less frequent administrations, which will reduce patient burden and increase patient compliance.

Modulating Boronic Ester Stability in Block Copolymer Micelles via the Neighbor Effect of Copolymerized Tertiary Amines for Controlled Release of Polyphenolic Drugs.

The traceless and pH-sensitive properties of boronic esters are attractive for the synthesis of polymer-drug conjugates, but current platforms suffer from both low stability under physiologically relevant conditions and synthetically demanding optimization to tune drug release profiles. We hypothesized that the high catechol affinity and stability of Wulff-type boronic acids could be mimicked by copolymerization of phenyl boronic acid with a tertiary amine and subsequent micellization. This strategy yielded a versatile platform for the preparation of reversible polymer-drug conjugates, which more than doubled the oxidative stability of encapsulated polyphenolic drug cargo at physiologically relevant pH and enabled simple and incremental tuning of drug release kinetics.

Design of Polymeric Carriers for Intracellular Peptide Delivery in Oncology Applications.

In recent decades, peptides, which can possess high potency, excellent selectivity, and low toxicity, have emerged as promising therapeutics for cancer applications. Combined with an improved understanding of tumor biology and immuno-oncology, peptides have demonstrated robust antitumor efficacy in preclinical tumor models. However, the translation of peptides with intracellular targets into clinical therapies has been severely hindered by limitations in their intrinsic structure, such as low systemic stability, rapid clearance, and poor membrane permeability, that impede intracellular delivery.

Glomerular disease augments kidney accumulation of synthetic anionic polymers.

Polymeric drug carriers can alter the pharmacokinetics of their drug cargoes, thereby improving drug therapeutic index and reducing side effects. Understanding and controlling polymer properties that drive tissue-specific accumulation is critical in engineering targeted drug delivery systems. For kidney disease applications, targeted drug delivery to renal cells that reside beyond the charge- and size-selective glomerular filtration barrier could have clinical potential.