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The ocular coil as drug delivery device: in vivo studies on safety and comfort, drug release and efficacy

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First Author: C.Bertens THE NETHERLANDS

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

Abstract Details

Purpose:

Currently, eye drops are the most prescribed therapy for treatment and prevention of ocular diseases, mainly because of their low costs. However, noncompliance and low drug absorption compromise the effectiveness of eye drops. Therefore, there is a need for improved ophthalmic drug delivery. The aim of our study is to evaluate the ocular coil (OC), a new drug delivery device which is inserted in the inferior conjunctival fornix. We investigated the safety of two versions of the ocular coil (straight and curved), its drug release characteristics and efficacy of the ketorolac-loaded OC.

Setting:

The human safety and comfort study was designed as a unilateral randomized intervention study and was performed at the University Eye Clinic Maastricht, Maastricht, the Netherlands. The animal studies were designed as randomized prospective studies, and were performed at the department of Ophthalmology, Maastricht University, Maastricht, the Netherlands.

Methods:

For the human study, OCs filled with non-drug loaded microspheres were inserted in two cohorts of 21 healthy volunteers for 28 days. Safety and comfort were evaluated through slit-lamp examinations and questionnaires. For the animal studies, OCs were filled with ketorolac-encapsulated microspheres. In vivo drug release was determined in tears, aqueous humor and blood of New-Zealand White rabbits and compared to eye drops. Efficacy was determined after paracentesis-induced ocular inflammation followed by treatment with the OC, ketorolac eye drops or no treatment. Concentrations of ketorolac and cytokines were determined in tears, aqueous humor, and blood using HPLC and ELISAs.

Results:

Both versions of the non-drug-loaded-OC were well tolerated and comfortably. No significant differences were observed in ocular redness. However, retention time was lower as expected, with a median retention time of 5 and 12 days for the straight and curved OC, respectively. Four hours after administration, a 28-fold higher concentration of ketorolac was found in tears of rabbits for the OC compared to eye drops. In aqueous humor and blood, the ketorolac concentration was 9 and 10-fold higher for the OC compared to eye drops, respectively. Both the OC and eye drops effectively reduce production of PGE2, IL-6, and TNFα.

Conclusions:

Treatment of inflammation using the OC compares to treatment using eye drops. However, treatment with the OC is without the burden of daily administration. Despite high safety and comfort, the retention time of the OC was lower than expected. Additional design changes are recommended in order to increase the retention time towards a period of 28 days.

Financial Disclosure:

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