Health
Polymer for needle-free insulin delivery
New polymer reported in nature This could be a turning point for needle-free insulin delivery. Researchers at Zhejiang University Developed charge-transfer polyzwitterions Transports insulin into the bloodstream through intact skin and has a powerful hypoglycemic effect in diabetic mice and minipigs (nature 2025DOI: 10.1038/s41586-025-09729-x).
According to co-author Youqing Shen, transdermal delivery typically only works for small hydrophobic molecules with a mass less than 500 Da. Larger molecules, including peptides, proteins, and virtually all polymers, are blocked by the dense lipid matrix of the stratum corneum, the outermost layer of the skin. This barrier is so effective that in cosmetic safety assessments, polymers above 1,000 Da are generally excluded from skin penetration studies, says Shen. A new study challenges that assumption by demonstrating that poly, a synthetic polymer.[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate]or OP, can efficiently cross the skin and carry insulin (approximately 5,800 Da) with the skin.
This polymer works by exploiting the skin's natural acidity, which changes from the surface down. Because the environment in the stratum corneum is slightly acidic, some of the surface lipids lose protons and become slightly negatively charged. OPs become positively charged under these acidic conditions and are therefore electrostatically attracted to negatively charged lipids. This attraction helps the OP to latch onto and slip between the oil layers of this barrier, which would normally block large molecules such as insulin.
A few layers deeper, the pH becomes neutral and the OP automatically switches to a globally neutral state of zwitterions. In this form, it no longer attaches to lipids or cell surfaces, but instead floats freely through the lower layers of the skin and eventually circulates throughout the body. Insulin bound to OP follows the same route, effectively hitchhiking past barriers it cannot cross on its own.
Researchers report that when OP was combined with insulin, it delivered enough hormone through the skin to normalize blood sugar levels in small and large test animals. In type 1 diabetic mice, topical OP insulin produced hypoglycemic effects comparable to injected insulin. When administered transdermally to diabetic minipigs, normal blood glucose levels were restored without causing skin inflammation or structural damage, even after repeated applications.
“This work represents an important advance that addresses a major challenge in drug delivery,” says Matthew Webber, a University of Notre Dame engineer and supramolecular materials expert who was not involved in the study.
Shen said the team is currently working with pharmaceutical partners to move the platform toward clinical development. Looking beyond insulin, the researchers hope that this strategy will enable transdermal delivery of other macromolecules, including therapeutic peptides and proteins, such as glucagon-like peptide-1 analogs.
“A safe, non-invasive insulin delivery system has the potential to dramatically improve the daily lives of people with diabetes,” Weber says.
If the technology proves safe and effective in humans, it could offer an alternative to daily injections and patch pumps for managing diabetes, opening up a new route for delivering drugs through intact skin. “Eliminating injections could reduce the pain, fear, and burden of treatment, making it easier for these people to adhere to treatment,” Weber says.
Chemistry & Engineering News
ISSN 0009-2347
Copyright © 2025 American Chemical Society
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Sources 2/ https://cen.acs.org/pharmaceuticals/drug-delivery/polymer-needle-free-insulin-delivery/103/web/2025/11 The mention sources can contact us to remove/changing this article |
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