ArticleProceedings of the National Academy of Sciences of the United States of America2015
Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers, 1 of them a synthesis that pooled it.
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Who cites it
254 citing papers in PubMed, 1 synthesis or guideline pooled it, 810 citations in OpenAlex.
- Non-transdermal microneedles for advanced drug delivery.Advanced drug delivery reviews · 2020Pooled it
- Hydrogel microneedles functioning in pathological surroundings: where soft materials overcome hard scars.Materials today. Bio · 2026Review
- A wearable closed-loop insulin micropump toward a miniaturized artificial pancreas for diabetes.Microsystems & nanoengineering · 2026Article
- Skin Barrier-Informed Topical and Transdermal Drug Delivery: Excipient-Driven Strategies, Vehicle Transformation, and Translational Challenges.Pharmaceutics · 2026Review
- Glucose-Responsive Nanomedicine in Diabetes Therapy: Emerging Advances and Clinical Prospects.Journal of functional biomaterials · 2026Review
- A Comprehensive Review on Engineering Release at the Molecular Level: Role of Functional Groups in Polysaccharide-Based Drug Delivery.Materials (Basel, Switzerland) · 2026Review
- Microneedle-based platforms for wound healing: recent advances.Journal of materials chemistry. B · 2026Review
- Polymeric microneedles for closed-loop drug delivery: from biosensing to therapy.RSC advances · 2026Review
- Highly cited original research in microneedle science from 2015 to 2025 a bibliometric and altmetric analysis.Discover nano · 2026Review
- Biomimetic Material Selection for Therapeutic Microneedles: An Analytic Hierarchy Process-Based Multi-Criteria Evaluation.Polymers · 2026Article
- Two-step distance tuning of TMaterials today. Bio · 2026Article
- pH and Glucose Dual-Responsive Hybrid Polymeric Smart Insulin Carrier for Diabetes Treatment.Polymers · 2026Article
- Development and Characterization of Ginsenoside-Aconitum Lipidic Cubic Nanoparticle-Loaded Dissolving Microneedles for Enhanced Transdermal Anti-inflammatory Therapy.AAPS PharmSciTech · 2026Article
- Biosensor-Integrated Microneedle Devices for Diagnosis and Treatment of Chronic and Infectious Diseases: Current Status, Trends and Challenges.Biosensors · 2026Review
- Microneedle Strategies for Diabetic Wound Management: A Comprehensive Review of Materials, Mechanisms, and Therapeutic Outcomes.Materials today. Advances · 2026Article
- Review
- A Wearable, Dual Closed-loop Insulin Delivery System for Precision Diabetes Management.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- [Advances in injectable and transdermal glucose-responsive insulin delivery systems].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Polymeric soft materials with molecular recognition: from static binding to dynamic functions in gels, particles, and interfaces.Science and technology of advanced materials · 2026Review
- Microneedle Delivery of Small Extracellular Vesicles From Young Blood to Treat Endothelial Senescence.Advanced materials (Deerfield Beach, Fla.) · 2026Article
194 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
A glucose-responsive "closed-loop" insulin delivery system mimicking the function of pancreatic cells has tremendous potential to improve quality of life and health in diabetics. Here, we report a novel glucose-responsive insulin delivery device using a painless microneedle-array patch ("smart insulin patch") containing glucose-responsive vesicles (GRVs; with an average diameter of 118 nm), which are loaded with insulin and glucose oxidase (GOx) enzyme. The GRVs are self-assembled from hypoxia-sensitive hyaluronic acid (HS-HA) conjugated with 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazoles through bioreduction under hypoxic conditions. The local hypoxic microenvironment caused by the enzymatic oxidation of glucose in the hyperglycemic state promotes the reduction of HS-HA, which rapidly triggers the dissociation of vesicles and subsequent release of insulin. The smart insulin patch effectively regulated the blood glucose in a mouse model of chemically induced type 1 diabetes. The described work is the first demonstration, to our knowledge, of a synthetic glucose-responsive device using a hypoxia trigger for regulation of insulin release. The faster responsiveness of this approach holds promise in avoiding hyperglycemia and hypoglycemia if translated for human therapy.
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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.