Safety and drug-release characteristics of the ocular coil: a new non-invasive drug-delivery device to prevent intraocular inflammation after cataract surgery

Session Details

Session Title: Cataract Surgery: Complications & Management

Session Date/Time: Tuesday 17/09/2019 | 14:00-16:00

Paper Time: 14:00

Venue: Free Paper Forum: Podium 1

First Author: : C.Bertens THE NETHERLANDS

Co Author(s): :    M. Gijs   S. van Uden   A. Dias   F. van den Biggelaar   R. Nuijts                 

Abstract Details

Purpose:

Noncompliance and low drug levels compromise the effectiveness of eye drops and ophthalmic ointments. Therefore, there is a need for improved ophthalmic drug delivery. The aim of our study is to evaluate the safety and drug release characteristics of the ocular coil, a new sustained drug delivery device which is inserted in the lower conjunctival fornix.

Setting:

The human comfort study was designed as a single-center, unilateral randomized intervention study and was performed at the University Eye Clinic Maastricht, Maastricht, the Netherlands. The animal study was designed as a randomized prospective pharmacokinetic study, and was performed at the department of Ophthalmology, Maastricht University, Maastricht, the Netherlands.

Methods:

Coils were prepared with ketorolac-encapsulated microspheres or placebo microspheres. Placebo-loaded coils were inserted in the lower conjunctival fornix of a cohort of 21 healthy volunteers for 28 days. Safety and comfort were evaluated through slit-lamp examination and questionnaires, respectively. The in vitro drug release profile of ketorolac-loaded coils was examined in a proprietary lacrimal flow-simulating set-up. The in vivo drug release was determined by inserting the coil in the lower conjunctival fornix of nine New-Zealand White rabbits, and compared to ketorolac-containing eye drops. Concentrations of ketorolac were determined in tears, aqueous humor, and blood using HPLC.

Results:

The placebo-loaded coil was well tolerated and scored high on comfort and safety. No significant differences were observed in conjunctival-redness and limbal-redness. In addition, no signs of blepharitis or Meibomian gland dysfunction were observed. The ketorolac-loaded coil showed burst release in vitro with a peak concentration of 130µg/mL after 4 hours. In vivo, a concentration of 17ng/µL ketorolac was found in tears after 4 hours. The detected concentration ketorolac in aqueous humor (278ng/mL) was about 3 times lower than eye drops (993ng/mL), whereas in blood (15ng/mL), the concentration was about 1.5 times higher compared to eye drops (11ng/mL).

Conclusions:

Despite high safety and comfort, the retention time was low. To increase the retention rate for the full period of 28 days, we adapted the design of the coil from straight to curved. Although the concentration of ketorolac in the eye is lower with the coil compared to eye drops, an efficacy study in New-Zealand White rabbits will show whether drug release from the coil is able to prevent a surgically induced ocular immune response.

Financial Disclosure:

None