Behind the Scenes: Microneedle Technology Improves Drug Delivery in the Eye
A number of chronic eye diseases treated by ophthalmologists, such as macular degeneration and glaucoma, require regular injections directly into the eye. Injections entail serious risks including patient discomfort, the possibility of infection and the potential damage to delicate eye structures.
Researchers have been investigating better solutions for drug delivery to patients. For example, a team from Nanyang Technological University in Singapore recently developed a small medicine-delivery patch that patients can place directly on their eyes, much like a contact lens.
The patches leave behind tiny needles that slowly dissolve into the eye and release ophthalmologic drugs in the process. The technology could reduce pain, minimize the cost of therapy and help prevent infection.
Delivering Drugs Directly to the Eye
The challenge of delivering drugs directly to the eye is not a new one. Systemic injections prove inefficient because not enough of the drug reaches the eye. Eye drops seem like an obvious solution. However, when drops are used, little of a drug is actually absorbed into the eye because of natural barriers. Additionally, the drops easily wash out so it is difficult to judge dosing.
Researchers have suggested hydrogels to maximize contact between drug and eye. Unfortunately, this does not mitigate the poor absorption issue. Another potential solution is implanting drug reservoirs in the eye. However, this is both risky and expensive. Microneedles, which are already used to deliver anesthetic, vaccines and other medications, could prove the ideal solution.
Early trials with microneedles as a means of delivering ophthalmologic drugs were not successful. These attempts used stainless steel needles coated with medication or extremely thin glass needles filled with the drug.
These early microneedle attempts introduced the medication quickly. As a result, the circulation of fluid in the eye clears most of the drug before it is absorbed. This problem led researchers to ask how the drug could be introduced slowly over time, which could actually treat chronic, degenerative conditions more effectively.
A New Microneedle Delivery System
The research team from Nanyang Technological University has produced its new delivery system using hyaluronic acid. This natural component of connective tissues in the body is also found in the eye’s vitreous fluid. Alone, this material would quickly dissolve on the wet surface of the eye’s cornea. To combat this, the researchers added an additional ingredient of methacrylic anhydride and bound the two substances together using ultraviolet light.
The resulting material can penetrate the epithelium and stroma of the eye before slowly dissolving to deliver the drug over the course of several days. The inside of the needles consist of pure hyaluronic acid. This layer dissolves quickly to release a payload of the drug within minutes.
The slowly dissolving outer layer maintains drug levels in the eye. The team noted it is possible to alter the structure of its microneedles to speed or slow the release of the drug depending on dosing needs.
So far, the team has only tested its microneedle patch in mice. However, the results are promising. A two-millimeter square patch containing nine microneedles was used on mice with corneal neovascularization. The patch delivered the monoclonal antibody DC101 and blocked further vessel growth in the cornea. Within a few days, the patch had decreased abnormal vessel growth by an average of 90 percent.
The researchers also used a simpler version of the patch containing only hyaluronic acid. This decreased neovascularization by about 50 percent, which is similar to earlier experiments using steel microneedles. It appears the new technology could provide a more effective solution to eye disease.
Moving Forward with Microneedle Drug Delivery Research
The next step would involve human trials to enable researchers to gather data on subjective side effects, such as pain. Fortunately, researchers noted none of the mice in the study showed signs of discomfort. Another concern is whether the device would affect vision, although since the device is transparent, the researchers believe the effect would be minimal.
The primary challenge in making the device ready for humans involves scaling it for use in the human eye, which has a thicker cornea than a mouse eye. A human patch would involve about 100 microneedles compared to the nine needles used in mice.
In addition, glaucoma, macular degeneration and other diseases treated with injections affect the retina, which is at the back of the eye, rather than the cornea. The microneedle technology may have to be modified to treat conditions affecting the retina, as opposed to those that affect the anterior chamber such as corneal neovascularization.
Researchers will have to determine whether drugs delivered to the cornea reach the retina in therapeutic quantities. If this is not the case, researchers believe it would be possible to make microneedles robust enough to penetrate the sclera and deliver drugs directly to the posterior chamber. Moving forward, it will be exciting to see how the clinical applications of this technology evolve.