Eye drops are relatively difficult to apply: one-sixth of glaucoma patients need assistance putting medicated eye drops into their eyes. Further, the eye drops can cause stinging and allergic reactions, and as glaucoma’s symptoms can be subtle, patients often feel little motivation to take their medications. The resulting poor patient compliance can lead to irreversible blindness. While drug-eluting contact lenses were first proposed in the 1960s, poor drug release profiles have plagued prototypes.
Now, a team of Boston-based researchers led by Joseph Ciolino and Daniel Kohane of the Massachusetts Institute of Technology report, in the January issue of Biomaterials (DOI: 10.1016/j.biomaterials.2013.09.032; p. 432), a dual-polymer contact lens that releases therapeutic doses of the potent glaucoma medication latanoprost in vivo for a month. The device starts with methafilcon (a copolymer of methyl methacrylate and hydroxyethyl methacrylate). The researchers then spin-coat a solution of latanoprost and poly(lactic-co-glycolic acid) (PLGA) onto the methafilcon lens blank to produce 20-, 40-, or 45-μm-thick polymer-drug films. After solvent removal, a round aperture is incised in the center, and a topcoat of methafilcon is then applied to the donut-shaped translucent film. Finally, a lathe turns the cylindrical methafilcon-PLGA/latanoprost-methafilcon sandwich into a lens.
To track the in vitro drug release kinetics, the research team assayed daily aliquots of phosphate buffer solution (PBS) into which they had placed the lenses. After an initial burst, the latanoprost release rate steadied. The researchers also fitted lenses to rabbit eyes and periodically checked the concentration of latanoprost in the aqueous humor. The concentration of absorbed medication remained constant from the 3rd until the 28th day, after which time the lenses were removed. The latanoprost concentration in the aqueous humor was the same as for eye drop use.
Earlier studies by the research team demonstrated that both the PLGA and encapsulation within the polymer hydrogel contribute to the release kinetics. PLGA is FDA-approved; it biodegrades into components found naturally in the human body and has well-known release kinetics. The device’s function is not materials-dependent, Kohane said. “Unlike other approaches where the drug was distributed throughout the lens, in our design there was a real advantage from its macroscopic nature. The larger an object is, the smaller its surface area to volume ratio and therefore the slower and more controlled its release is going to be. The key concept here is the design rather than the specific materials.” While one concern for commercialization of the contact lens is degradation during storage, the PLGA can in principle be switched with a polymer with a longer shelf life.
Nor is the lens substrate materials-critical. In the long term the team may switch to contemporary silicone hydrogel lenses. For now they will try to increase the size of the film “window.” Currently the aperture is equivalent to that of eye-color-changing contact lenses, but the researchers want the light transmission to be close to that of vision-correcting lenses.
“Here you have a contact lens that could be built with the patient’s refractive correction, so that the patient would be seeing better using the lens.... Right now patients don’t have much incentive to be compliant with their glaucoma medications. Glaucoma is commonly asymptomatic so most patients don’t appreciate any vision loss until it’s too late. So I think something that adds an incentive that is currently not there would be beneficial to improving compliance,” said Ciolino.
Anuj Chauhan of the University of Florida uses vitamin E to slow contact lens drug release. “The strength of [the Boston] work is that you can release the medication for a month at zero-order release rates. Vitamin E is not zero order, it’s diffusion-controlled. The advantage of the thin films is that you get close to zero-order release. Other methods have their own advantages, and it’s good that multiple people are working on the problem.”
