A New Skin-Permeable Polymer Brings Us Closer to Needle-Free Insulin Delivery

A team of researchers has demonstrated a promising new way to deliver insulin through the skin without needles, using a specially designed polymer that moves insulin deep into the body while keeping the skin barrier fully intact. The work, recently published in Nature, shows successful results in both diabetic mice and minipigs, raising hopes for a future where managing diabetes becomes easier, less painful, and far more convenient.

The core of this breakthrough is a fast-penetrating polymer called poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate], referred to as OP. This polymer has a unique ability to travel through multiple layers of skin by interacting with the skin’s natural pH gradient. When paired with insulin, OP not only helps the hormone cross the skin but also ensures that it reaches the bloodstream and accumulates in key glucose-regulating organs such as the liver and skeletal muscles.

In controlled studies, applying the OP–insulin mixture directly onto the skin of diabetic mice and minipigs successfully lowered their blood glucose to normal ranges within 1–2 hours, a speed comparable to traditional insulin injections. Even more impressive, the glucose remained stable for up to 12 hours after application. Throughout the experiments, researchers observed no damage to the skin structure, no irritation, and no negative effects on blood cells, liver function, or kidney function. Importantly, insulin maintained its biological activity after being transported through the skin.

This development opens the door not just for insulin delivery but potentially for the noninvasive delivery of other large therapeutic molecules—something currently limited by the skin’s natural resistance to big proteins and peptides. While this method is still in preclinical stages and requires further investigation into long-term safety, dosage control, and real-world clinical effectiveness, the findings offer a compelling foundation for a new class of treatments.

How This Polymer Actually Works

The polymer OP is engineered to respond to changes in pH, a feature that skin naturally provides. Human (and animal) skin is slightly acidic on the surface but becomes more neutral with depth. This gradual pH shift allows OP to change its charge state as it travels downward.

On the outer surface of the skin, where the environment is more acidic, OP becomes positively charged. This charge helps it bind tightly to the skin’s surface lipids. As it moves into deeper layers, the polymer encounters a more neutral pH and shifts into a form that is electrically neutral. Once that happens, it releases itself from those surface bindings and continues moving freely through the epidermis and dermis, carrying insulin along with it.

Because this mechanism relies on natural skin chemistry and not mechanical disruption, it represents a noninvasive and structure-preserving form of drug delivery. No microneedles, no abrasion, and no ultrasound are required—just the chemical design of the polymer itself.

What the Experiments Showed

The research team tested OP–insulin on two types of animal models that represent different aspects of diabetes research.

Diabetic Mice

• OP–insulin lowered extremely high blood glucose to normal levels within an hour.
• The effect was sustained for several hours longer than the typical response from injected insulin in the same models.
• Fluorescent tracking confirmed that OP successfully carried insulin across all skin layers and into circulation.

Diabetic Minipigs

Minipigs more closely resemble human skin structure, making them ideal for this stage of testing.

• Blood glucose normalized within 1–2 hours of topical application.
• Normal glucose levels were maintained for up to 12 hours.
• The skin remained undamaged, with no inflammation, redness, or structural compromise.
• Internal organ assessments showed no toxicity and no adverse reactions.

Because both sets of results were consistent—and because minipigs provide more human-like data—researchers are optimistic about clinical potential. Still, human trials will be necessary before any medical product can be approved.

Why This Breakthrough Matters

People with diabetes who rely on insulin therapy often face multiple injections per day. Over time, this routine can cause:

• Skin irritation
• Scar tissue buildup
• Infection risks
• Reduced adherence to treatment due to discomfort or needle fear

A noninvasive option like an insulin patch or cream could significantly reduce these burdens. This is especially true for children, older adults, and individuals who struggle with injection self-management.

Furthermore, prolonged glucose stability—like the 12-hour effect seen in the study—could reduce dangerous highs and lows, potentially improving overall metabolic control and quality of life.

If OP proves safe and effective in humans, it may also be re-engineered for other large biological medicines currently limited to injections, including:

• Peptide hormones
• Protein-based therapies
• Certain vaccines
• Other biologics that cannot pass through skin naturally

This could help revolutionize how we deliver a wide range of treatments.

What Still Needs to Be Studied

Although the findings are promising, several questions must be addressed before OP–insulin can become a real-world therapy.

Long-Term Safety

Short-term animal tests showed no irritation or organ damage, but long-term exposure needs evaluation.

Dosing Consistency

Human skin varies widely from person to person. Factors such as skin hydration, temperature, oil levels, and thickness could influence absorption rates.

Manufacturing and Formulation

A stable, user-friendly product (patch, gel, or cream) must be developed and tested for shelf life, consistency, and ease of use.

Human Clinical Trials

Only robust, large-scale trials can confirm:

• Effectiveness
• Predictability
• Long-term impact
• Safety across different patient populations

Until then, OP remains a powerful proof of concept—but not yet a clinical reality.

Additional Background: Why Skin Is So Hard to Penetrate

To appreciate the importance of this work, it helps to understand why delivering big molecules like insulin through skin is unusually difficult.

Skin is designed by nature to keep foreign substances out. The toughest part to cross is the stratum corneum, a dense layer of dead cells packed in lipids. This structure only allows very small, nonpolar molecules to pass. Think nicotine patches, hormone patches, or small pain-relief molecules.

Large molecules—like insulin—are:

• Too big
• Too water-soluble
• Unable to cross the lipid matrix

Because of that, injectable delivery has remained the only viable option for decades.

Earlier attempts to bypass this included:

• Microneedles
• Chemical enhancers
• Ultrasound-assisted delivery
• Skin abrasion devices

But these approaches can be invasive, irritating, or inconsistent.

That’s what makes OP so intriguing—it creates a path through the skin without damaging it.

Additional Background: The Rising Demand for Better Insulin Delivery

Globally, diabetes continues to rise, and so does the demand for patient-friendly insulin delivery systems. Many people dislike injections or struggle with self-administration. A needle-free option could:

• Improve adherence
• Reduce complications
• Make insulin more accessible
• Lower long-term healthcare costs

Innovations like continuous glucose monitors (CGMs) and automated insulin pumps have already improved diabetes care. A breakthrough in noninvasive insulin delivery could complement these technologies and make diabetes management even smoother.

Research Paper Source

A Skin-Permeable Polymer for Non-Invasive Transdermal Insulin Delivery
https://doi.org/10.1038/s41586-025-09729-x