ArticleScience translational medicine2020
An ultrafast insulin formulation enabled by high-throughput screening of engineered polymeric excipients.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 66 citations in OpenAlex.
- Pharmacokinetics and Pharmacodynamics of a Novel U500 Insulin Aspart Formulation: A Randomized, Double-Blind, Crossover Study in People With Type 1 Diabetes.Diabetes care · 2023Trial
- Monomeric Insulin Analog and Stabilizing Excipient Enabled Ultrafast Insulin Formulation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Exploring the Holdase Activity of Supramolecular Chaperones with Amyloid-Forming Peptides and Insulin.Biomacromolecules · 2026Article
- Structure-Based Prediction of Molecular Interactions for Stabilizing Volatile Drugs.Pharmaceutics · 2026Article
- Ultrahigh-concentration biologic therapeutics enabled by spray drying with a glassy surfactant excipient.Science translational medicine · 2025Article
- Ionic liquids as stabilisers of therapeutic protein formulations: a review of insulin and monoclonal antibodies.Biophysical reviews · 2025Review
- Defining Structure-Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra-Stable Biopharmaceuticals.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Barcoded screening identifies nanocarriers for protein delivery to kidney.Nature communications · 2025Article
- Insulin Analogs and the Mode of Insulin Delivery: Recent Advances and Challenges.Current pharmaceutical biotechnology · 2025Review
- Applied machine learning as a driver for polymeric biomaterials design.Nature communications · 2023Review
- Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition.Acta pharmaceutica Sinica. B · 2023Review
- Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Random Heteropolymer Excipients Improve the Colloidal Stability of a Monoclonal Antibody for Subcutaneous Administration.Pharmaceutical research · 2023Article
- Stable High-Concentration Monoclonal Antibody Formulations Enabled by an Amphiphilic Copolymer Excipient.Advanced therapeutics · 2023Article
- New Injection Site Dynamics of Insulin Lispro Discovered Through Photoacoustic Imaging.Journal of diabetes science and technology · 2023Article
- Discrete, Chiral Polymer-Insulin Conjugates.Journal of the American Chemical Society · 2022Article
- Formulation Excipients and Their Role in Insulin Stability and Association State in Formulation.Pharmaceutical research · 2022Article
- Extreme Extensibility in Physically Cross-Linked Nanocomposite Hydrogels Leveraging Dynamic Polymer-Nanoparticle Interactions.Macromolecules · 2022Article
- Poly(trehalose methacrylate) as an Excipient for Insulin Stabilization: Mechanism and Safety.ACS applied materials & interfaces · 2022Article
- Immunostimulatory Polymers as Adjuvants, Immunotherapies, and Delivery Systems.Macromolecules · 2022Review
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Insulin has been used to treat diabetes for almost 100 years; yet, current rapid-acting insulin formulations do not have sufficiently fast pharmacokinetics to maintain tight glycemic control at mealtimes. Dissociation of the insulin hexamer, the primary association state of insulin in rapid-acting formulations, is the rate-limiting step that leads to delayed onset and extended duration of action. A formulation of insulin monomers would more closely mimic endogenous postprandial insulin secretion, but monomeric insulin is unstable in solution using present formulation strategies and rapidly aggregates into amyloid fibrils. Here, we implement high-throughput-controlled radical polymerization techniques to generate a large library of acrylamide carrier/dopant copolymer (AC/DC) excipients designed to reduce insulin aggregation. Our top-performing AC/DC excipient candidate enabled the development of an ultrafast-absorbing insulin lispro (UFAL) formulation, which remains stable under stressed aging conditions for 25 ± 1 hours compared to 5 ± 2 hours for commercial fast-acting insulin lispro formulations (Humalog). In a porcine model of insulin-deficient diabetes, UFAL exhibited peak action at 9 ± 4 min, whereas commercial Humalog exhibited peak action at 25 ± 10 min. These ultrafast kinetics make UFAL a promising candidate for improving glucose control and reducing burden for patients with diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.