From plugs to pumps, innovative drug delivery systems are in the pipeline to aid us in overcoming one of the biggest challenges in glaucoma care: lack of compliance.

PLUGS AND INSERTS

Ocular Therapeutix has been working on a drug-eluting punctum plug that contains travoprost. The travoprost molecules are released by hydrolysis from microspheres that are suspended in a biodegradable hydrogel rod. This plug can provide sustained release of travoprost over 2 to 3 months. The company also has a similar product for delivery of dexamethasone and moxifloxacin.

To-scale size comparison of a punctum plug depot from Ocular Therapeutix.

Mati Therapeutics is developing the Evolute punctal plug drug delivery system (PPDS), which delivers latanoprost over a period of 2 to 3 months.

The punctal drug delivery system from Mati Therapeutics.

Amorphex Therapeutics has developed the Topical Ophthalmic Drug Delivery Device, or TODDD, which is a contact lens-like device that sits on the sclera, underneath the upper eyelid, and can hold a large volume of medication or even multiple medications at a time for long-term release. The device is made out of polymers that are biocompatible and well tolerated. The drug can then be delivered over a period of 3 months or more.

OTHER INNOVATIONS

Several other innovations in the delivery of glaucoma medications are emerging.

Pentablock copolymers are biomaterials that can serve as a vehicle for topical and intraocular drug delivery. Nanoparticles of drug can be suspended in the pentablock thermosensitive gel. For glaucoma purposes, a drug, combined with the pentablock copolymer, would be topically applied to the eye and, once exposed to body temperature, would transform from a solution into a gel. The gel stays underneath the eyelid as a film and gradually releases the medication. The copolymer was developed and is being studied by Ashim K. Mitra, PhD, and colleagues at the University of Missouri.

Verisome (Icon Bioscence) is a biodegradable platform being studied for latanoprost delivery over 6 months after injection into the anterior chamber with a 30-gauge needle. The technology is also being investigated for delivery of a medication for retinoblastoma and intravitreal delivery of triamcinolone acetonide.

Pfizer partnered with pSivida (the developer of Iluvien and Retisert) to develop Durasert, which is a bioerodible drug delivery system for latanoprost. Durasert contains latanoprost and can be injected into the subconjunctival space with a 25-gauge needle to provide a low daily dose of the medication for a longer period of time.

DuraSite (InSite Vision) is another vehicle polymer used in commercially available eye drops (Azasite [Inspire Pharmaceuticals] and Besivance [Bausch + Lomb]). DuraSite is currently being studied for bimatoprost topical delivery and was found to improve drug delivery in rabbit eyes compared with Lumigan drops (Allergan).¹ It can maintain therapeutic doses of a drug on the ocular surface for up to 6 hours.

PUMP

There is at least one pump system for glaucoma therapy in the pipeline as well. Replenish is developing an ophthalmic micropump system that consists of a small, automated, refillable drug pump that is implanted on the sclera. The pump can inject programmed amounts of drug at set times and can hold up to a year’s worth of medication.

SUMMARY

There are many advantages to delivering glaucoma medical therapy in a reliable and intelligent way: improvement in the patient’s quality of life; better, more continuous IOP control with fewer side effects by utilizing lower doses of medication, etc. Imagine connecting a “smart” drug delivery system to a 24-hour IOP monitor and providing medication in the quantity and frequency needed to halt progression in a particular patient with a specific disease stage and therapeutic needs. I believe it is our generation of ophthalmologists that will get to enjoy a new way to practice glaucoma care!

1. Bowman L, Shafiee A, Hou E, Hosseini K. Ocular pharmacokinetics of ISV-215 (Bimatoprost 0.03%) formulated in a DuraSite delivery system compared to Lumigan in rabbits. Poster presented at: the Association for Research in Vision and Ophthalmology Annual Meeting; May 5-9, 2013; Seattle, Washington.