Core–Shell DOX-Loaded PLGA Electrospun Membrane Enables Sustained Local Drug Delivery for Preventing Postoperative Fibrosis after Glaucoma Filtration Surgery

Glaucoma is a silent thief of sight, a condition where pressure builds up inside the eye and slowly damages the optic nerve. To stop this pressure from rising, surgeons often perform a filtration operation, creating a tiny new drainage channel that allows fluid to escape. However, the human body is designed to heal wounds, and in this delicate surgery, that natural instinct becomes the enemy. As the eye repairs the incision, scar tissue forms over the new drainage hole, sealing it shut and causing the surgery to fail. For decades, doctors have tried to stop this scarring by applying powerful drugs that kill the fast-growing cells responsible for the scar. Yet, these drugs are a double-edged sword; they are so toxic that they can damage healthy tissue, and they wash away too quickly to do their job long enough. The challenge has been finding a way to deliver a precise, gentle dose of medicine right where it is needed, keeping it there just long enough to stop the scar without hurting the eye.

Researchers at the First Affiliated Hospital of Fujian Medical University and Shanghai Ninth People's Hospital have developed a new approach to solve this problem. Instead of applying a liquid drug that disappears quickly, they created a microscopic, flexible membrane that acts like a slow-release patch. This membrane is made of a safe, biodegradable plastic known as poly(lactic-co-glycolic acid), or PLGA, which the body can naturally break down over time. Inside this plastic shell, they trapped doxorubicin, a potent drug known for stopping cell growth. The key innovation lies in how they built it. Using a technique called coaxial electrospinning, which shoots a fine stream of liquid through an electric field to spin it into fibers, they created a structure where the drug is hidden in the core and the plastic forms the outer layer. This design protects the drug and ensures it leaks out slowly and steadily, rather than all at once.

To test if this idea worked, the team first looked at how the drug affected conjunctival fibroblasts, the specific cells that build scar tissue in the eye. They found that the drug successfully stopped these cells from multiplying and moving, but only at certain concentrations. If the dose was too high, it killed the cells too aggressively, which could be dangerous. If it was too low, it had no effect. They settled on a specific concentration that stopped the cells effectively without causing excessive damage. Next, they examined the membrane itself under a microscope. The fibers were smooth and uniform, and chemical tests confirmed that the drug was successfully trapped inside the plastic. When they placed the membrane in a simulated eye environment, it released the drug steadily over several days, reaching a point where about two-thirds of the drug had been delivered after eighty hours, and then leveling off. This slow release is crucial because it keeps the drug active during the critical weeks when the eye is trying to heal.

The researchers then moved to a living model, performing the filtration surgery on rabbits to see how the membrane worked in a real biological system. They divided the animals into three groups. One group received a plain plastic membrane with no drug. A second group received a sponge soaked in the drug, which was applied to the eye for a few minutes and then rinsed away, mimicking the current standard of care. The third group received the new drug-loaded membrane. The results were striking. In the group with the plain membrane, the drainage hole quickly became blocked by scar tissue, and the eye pressure rose back to dangerous levels within a few days. The group with the soaked sponge did slightly better, but the drug washed away too fast, and the scarring eventually took over, with the drainage hole failing after about ten days.

In contrast, the rabbits with the drug-loaded membrane showed a completely different outcome. The drainage holes remained open and functional for much longer, with the average survival time of the surgical site extending to nearly twenty days. The eye pressure in these animals stayed low and stable, averaging just under ten millimeters of mercury twenty-eight days after the surgery, a significant improvement over the other groups. Crucially, the membrane did not cause harm. The researchers checked for signs of inflammation, infection, or damage to the clear cells on the surface of the eye, known as the cornea, and found none. The drug was contained within the membrane, acting locally where it was needed, and did not spread to cause toxicity in the heart or other parts of the body.

This study suggests that embedding a drug into a slow-release, biodegradable membrane offers a safer and more effective way to prevent scarring after glaucoma surgery than current methods. By keeping the drug in place and releasing it gradually, the membrane stops the scar tissue from forming without the high toxicity associated with traditional drug applications. While the researchers note that more studies are needed to refine the timing and dosage for human use, the work demonstrates a clear path forward. It transforms a difficult medical problem into a manageable engineering solution, offering hope that future surgeries could succeed more often, preserving vision for patients who currently face the risk of their eyes healing themselves back into blindness.