Innovative Approach Paves Way for Insulin Delivery Through the Skin

Researchers are exploring new possibilities for administering insulin through the skin, potentially offering an alternative to injections for diabetes management. A team from Zhejiang University in Hangzhou, China, has developed a novel approach that utilizes a specialized polymer to transport insulin transdermally.

The focus of the research is on a zwitterionic polymer known as poly[2-(N-oxid-N,N-dimethylamino)ethyl methacrylate], abbreviated as OP. This polymer exhibits unique charge-switching properties depending on the pH of its environment. In the skin's outermost layers, which are more acidic, OP is positively charged, enabling it to bind effectively to the lipid-rich stratum corneum. As the polymer penetrates deeper into neutral pH regions of the skin, it loses its charge, detaches from the lipids, and facilitates the release of its insulin payload into the bloodstream.

To assess the effectiveness of this delivery system, the researchers coupled human insulin with the OP polymer and compared its skin permeability to that of insulin attached to polyethylene glycol (PEG) and unmodified insulin. Laboratory studies using skin models demonstrated that OP-linked insulin was able to traverse the outer skin barrier and reach deeper layers within four hours of application. In contrast, both PEG-linked and native insulin remained confined to the skin's surface.

Further tests were conducted using animal models, including mice with type 1 diabetes and minipigs. In diabetic mice, the topical application of OP-bound insulin reduced blood glucose levels to normal within one hour, with the effect lasting for up to twelve hours. Similarly, in minipigs, a topical OP-insulin cream normalized blood sugar within two hours, maintaining stable levels for the same duration. Topically applied PEG-insulin and unmodified insulin showed no significant effects in these trials.

Additional analyses indicated that OP-linked insulin retained the same affinity for insulin receptors as standard insulin. Importantly, topical application did not cause skin irritation or inflammation, nor were any signs of systemic toxicity observed in the animal studies.

While these results highlight the potential of OP as a vehicle for transdermal insulin delivery, its applicability in humans remains to be established. Current findings are limited to animal studies, and further research is necessary to determine whether similar outcomes can be achieved in people. Key questions include whether human skin will allow sufficient insulin absorption, how quickly and for how long insulin delivered this way will act, as well as safety considerations such as immune responses and long-term effects. The consistency and reproducibility of the delivery method must also be evaluated in future studies.

Beyond diabetes therapy, the OP polymer could hold promise for the transdermal delivery of other protein- and peptide-based drugs that are currently unsuitable for skin application. Many of these molecules, like insulin, have historically required injections due to their inability to penetrate the skin barrier effectively.

The research represents an important step towards needle-free insulin administration and could pave the way for new treatment options for various conditions that require protein or peptide therapeutics. However, extensive clinical validation will be essential before such technology can be considered for human use.