Sticky Solutions from the Sea: A Mussel-Inspired Patch That Could Replace Daily Pills

What do marine mussels and thyroid medication have in common? Until recently, not much. But now, in a creative leap from the shoreline to the stomach, researchers have drawn inspiration from mussel adhesion to engineer a long-acting gastric patch for drug delivery—potentially transforming how chronic conditions like hypothyroidism are managed.

At the heart of this innovation lies a deceptively simple question: what if a single oral dose could last for weeks, or even a month? In the case of levothyroxine sodium (LT)—the go-to therapy for hypothyroidism—the answer may lie in mucoadhesive chemistry and a little help from nature’s best glue artist. This research was led by Prof. Venkata Vamsi Krishna Venuganti and his students Srivarsha Reddy Bollareddy & Shreya Shashank Chauhan at the Department of Pharmacy, BITS Pilani – Hyderabad Campus.

The Adherence Problem in Oral Drug Delivery

Oral tablets and capsules are convenient, but they come with limitations—especially for drugs with poor solubility, low permeability, or short gastric residence times. Levothyroxine, despite being prescribed to millions worldwide, has a bioavailability of just 40–80% in humans. It is sensitive to food intake, exhibits erratic absorption, and must be taken on an empty stomach. This makes daily adherence challenging, and missing doses can quickly lead to suboptimal thyroid levels.

To address this, the study by Bollareddy et al. (2025) introduces a bioinspired, three-layered gastric patch that adheres to the stomach lining and releases levothyroxine consistently over 30+ days. The innovation isn’t just about holding onto medication—it's about holding onto the stomach lining, long enough to overcome the rapid mucus turnover that usually pushes foreign materials out in hours.

Inspired by Mussels, Engineered for Mucoadhesion

Mussels adhere to wet rocks in turbulent ocean environments using sticky proteins rich in catechol groups, particularly DOPA (3,4-dihydroxyphenylalanine). Mimicking this, the research team designed a mucoadhesive layer based on 4-carboxyphenylboronic acid (CPBA) conjugated to chitosan. CPBA’s boronic acid groups form transient covalent and hydrogen bonds with sialic acid residues on the mucosal surface—similar to the mussel’s mechanism.

This CPBA-chitosan conjugate demonstrated impressive mucoadhesion strength of 25 ± 1.1 kPa—the highest reported to date for a gastric patch. For comparison, earlier patches using hydrocaffeic acid had a max adhesion of around 18 kPa. This stronger grip allows the patch to resist gastric motility, mucus turnover, and shear forces from chyme movement.

A Three-Layered Strategy

The patch comprises three functional layers:

1. Core Layer: This contains the drug—levothyroxine—and a carefully selected blend of hydrophilic (e.g., Carbopol 934P, HPMC K100M) and hydrophobic polymers (e.g., polycaprolactone, Eudragit RS100) that ensure zero-order release. This design controls drug diffusion and maintains structural integrity in acidic gastric fluid.

2. Mucoadhesive Layer: Coated with CPBA-chitosan, it binds to the gastric mucosa and keeps the patch anchored in place.

3. Backing Layer: A hydrophobic surface made from a polycaprolactone-siloxane composite that prevents adhesion to non-target tissues and blocks drug release from the non-mucoadhesive side.

Together, these layers create a directional, sustained release system—delivering levothyroxine through the mucosa-facing side while shielding the rest of the gastrointestinal tract.

Long-Acting Performance in Animal Models

The patch was tested in Sprague-Dawley rats, where it was administered orally using a gelatin capsule. Once released in the stomach, the patch adhered to the body region of the gastric mucosa and remained in place for over 30 days. Plasma levels of levothyroxine remained within a steady range (87–126 ng/mL) for up to 38 days after a single dose—eliminating the need for daily pills.

Importantly, the patch did not trigger any significant inflammatory response. Markers such as TNF-α, IL-1β, and IL-6 showed no statistically significant difference between control and patch-administered groups. Histological examinations of the stomach tissue confirmed the absence of damage or irritation under and around the patch area.

Stable, Scalable, and Simple

The patches demonstrated mechanical robustness (tensile strength ~3.6 MPa), retained mucoadhesive integrity, and remained stable at 5 ± 3 °C for at least six months—crucial for storage and transport.

Fabrication was achieved via a simple compression-based technique (1 kN force), significantly milder than traditional tablet manufacturing (10–15 kN), minimizing stress on sensitive ingredients. This makes the patch not only effective, but also scalable for clinical translation.

A Platform for the Future

While this study focused on levothyroxine, the implications extend far beyond. This gastric patch is a platform technology—its mucoadhesive design and directional release mechanism could be adapted for other drugs requiring sustained delivery in the GI tract, including those for chronic pain, hormonal regulation, or chemotherapy. By blending biomimicry with polymer engineering, this work exemplifies how “sticky science” can solve longstanding problems in medicine. Sometimes, the best innovations really do come from thinking like a mussel—cling on tightly, and never let go.