University Eye Clinic Maastricht, Maastricht University Medical Center+, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands; Maastricht University, School for Mental Health and Neuroscience, University Eye Clinic Maastricht, Universiteitssingel 50, P.O. Box 616, 6200 MD Maastricht, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), Gaetano Martinolaan 63-65, 6229 GS Maastricht, the Netherlands.
Eindhoven University of Technology (TU/e), Department of Chemical Engineering & Institute for Complex Molecular Systems (icms) and Chemistry, Laboratory of Physical Chemistry, P.O. Box 513, 5600 MB Eindhoven, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), Gaetano Martinolaan 63-65, 6229 GS Maastricht, the Netherlands.
Eur J Pharm Biopharm. 2020 May;150:120-130. doi: 10.1016/j.ejpb.2020.03.010. Epub 2020 Mar 12.
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.
眼用滴剂和眼膏是最常被用于眼部药物递送的方法。然而,由于药物生物利用度低、药物消除迅速以及患者顺应性低,因此需要改进眼部药物递送系统。本研究提供了一种新的药物递送装置的设计思路,该装置由充满载有酮咯酸的 PMMA 微球的眼用线圈组成。共制备了 9 种不同的眼用线圈,其线径和线圈外直径不同。基于其微球容纳能力和柔韧性,选择了一种类型的眼用线圈用于进一步实验。在将眼用线圈弯曲至曲率半径时,未观察到微球的逸出,该曲率半径反映了在体内将其定位在下结膜囊时的情况。通过将眼用线圈插入人尸体下穹窿结膜后进行 CT 成像,研究了其形状行为和组织接触情况。由于其高柔韧性,眼用线圈沿着眼球的圆周弯曲。由于其位于穹窿深部,因此在体内,眼用线圈似乎不太可能干扰眼球运动。体外药物释放实验表明,眼用线圈作为眼部持续药物递送装置具有潜力。我们开发了载有 26.5±0.3wt%酮咯酸的 PMMA 微球。在体外泪液系统中测试 28 天后,从眼用线圈中释放了 69.9±5.6%的负载酮咯酸。在前三天观察到较高的释放剂量(48.7±5.4%),随后酮咯酸的释放逐渐增加。因此,眼用线圈似乎是术后早期眼科药物递送的有前途的载体。