Long-term intraocular pressure reduction with intracameral polycaprolactone glaucoma devices that deliver a novel anti-glaucoma agent

Abstract

Long-term treatment of glaucoma, a major leading cause of blindness, is challenging due to poor patient compliance. Therefore, a drug delivery device that can achieve drug release over several months can be highly beneficial for glaucoma management. Here, we evaluate the long-term pharmacokinetics and therapeutic efficacy of polycaprolactone intracameral drug delivery devices in rabbit eyes. Our study showed that a single drug delivery device loaded with a proprietary hypotensive agent, DE-117, reduced intraocular pressure in normotensive rabbits significantly for 23weeks. In addition, we demonstrated that concentration of DE-117 and its hydrolyzed active form (hDE-117) was maintained in the aqueous humor and the target tissue (iris-ciliary body) up to 24weeks. Our proof-of-concept glaucoma implant shows potential as a long-term treatment that circumvents patient compliance barriers compared to current treatment via eye drops.

24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients

“…By providing sustained IOP-lowering effects, drug-delivery systems such as Bimatoprost SR may help to address this unmet need. These new delivery systems may delay the need for more invasive (surgical) treatment by more precisely targeting the drug to sites of action [30,35,36], while providing IOP-lowering effects and tolerability profiles comparable to those of topical therapy [28,37,38]. Other sustained-release products are in various phases of clinical development, including ENV515 (Envisia Therapeutics, Durham, NC, USA), OTX-TIC (Ocular Therapeutix, Bedford, MA, USA), and iDose (Glaukos Corporation, Laguna Hills, CA, USA) for intracameral delivery of travoprost.…”

Sustained drug delivery platforms – A new era for glaucoma treatment

“…[45] In a more recent study in 16 normotensive rabbits, the same group found a statistically significant IOP reduction in eyes implanted with the DE-117 PLC compared with untreated eyes and placebo PCL devices. [46] Tolerability was good and rates of iris trauma and hyphema during the implantation procedure were lower (19%) than in the previous study (29%). One DE-117 implant migrated to the angle, but this had no obvious effect on its activity.…”

Pharmacokinetic Simulations of Intravitreal Biologicals: Aspects of Drug Delivery to the Posterior and Anterior Segments

“…Long acting intracameral implants have been developed as an alternative for the use of anti-glaucoma eyedrops that have poor patient compliance in the clinical practice [34,35]. Biologicals cannot be used as eyedrops for anterior segment treatments, because they do not permeate across the cornea and the bioavailability after sub-conjunctival delivery is less than 10% [7].…”

“…Furthermore, the aqueous humor bioavailability of an intravitreal protein drug is almost complete, because nearly a whole dose is eliminated via the anterior route. Sampling of aqueous humor has also been used as an indicator of drug activity for intravitreally administered protein drugs, which also applies in humans [34].…”