Design of the ocular coil, a new device for non-invasive drug delivery

Christian J.F. Bertens (Corresponding author), Chiara Martino, Marty C. van Osch, Arno Lataster, Aylvin J.A.A. Dias, Frank J.H.M. van den Biggelaar, Remco Tuinier, Rudy M.M.A. Nuijts, Marlies Gijs

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Eye drops and ointments are the most prescribed methods for ocular drug delivery. However, due to low drug bioavailability, rapid drug elimination, and low patient compliance there is a need for improved ophthalmic drug delivery systems. This study provides insights into the design of a new drug delivery device that consists of an ocular coil filled with ketorolac loaded PMMA microspheres. Nine different ocular coils were created, ranging in wire diameter and coiled outer diameter. Based on its microsphere holding capacity and flexibility, one type of ocular coil was selected and used for further experiments. No escape of microspheres was observed after bending the ocular coil at curvature which reflect the in vivo situation in human upon positioning in the lower conjunctival sac. Shape behavior and tissue contact were investigated by computed tomography imaging after inserting the ocular coil in the lower conjunctival fornix of a human cadaver. Thanks to its high flexibility, the ocular coil bends along the circumference of the eye. Because of its location deep in the fornix, it appears unlikely that in vivo, the ocular coil will interfere with eye movements. In vitro drug release experiments demonstrate the potential of the ocular coil as sustained drug delivery device for the eye. We developed PMMA microspheres with a 26.5 ± 0.3 wt% ketorolac encapsulation efficiency. After 28 days, 69.9% ± 5.6% of the loaded ketorolac was released from the ocular coil when tested in an in vitro lacrimal system. In the first three days high released dose (48.7% ± 5.4%) was observed, followed by a more gradually release of ketorolac. Hence, the ocular coil seems a promising carrier for ophthalmic drugs delivery in the early postoperative time period.

Original languageEnglish
Pages (from-to)120-130
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume150
DOIs
Publication statusPublished - May 2020

Funding

This research was performed under the framework of the Chemelot Institute for Science and Technology (InSciTe). We would like to express our gratitude to Mr. Bernard Uihlein and Mr. Timo Gneiting from EPflex, Dettingen an der Erms, Germany for their support. We would also like to express our gratitude to prof. dr. Christine Jérôme from the University of Liège for the production of the drug encapsulated microspheres. Furthermore, we thank colleagues at the department of Radiology of the Maastricht University Medical Center +, for the assistance and set-up of the CT-scan. We thank Sofie van Uden for her collaboration with the design of the in vitro lacrimal system. We would also like to thank dr. Chris Duxbury for proofreading the manuscript. The research was conducted within the Chemelot InSciTe framework. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

FundersFunder number
Chemelot Institute for Science and Technology
Weill Cornell Medical College
Université de Liège

    Keywords

    • Drug delivery
    • Drug delivery system
    • Microspheres
    • Ocular coil
    • Ophthalmology

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