Three-dimensional-printed Refillable Drug Delivery Device for Long-term Sustained Drug Delivery to Retina

Abstract

As the aging population increases worldwide, the number of patients with retinal diseases requiring long-term treatment, such as for age-related macular degeneration (AMD), is expected to increase. Intravitreal injection is the most common clinical treatment method for AMD, but a less invasive method and continuous drug administration are desirable. Here, we report a 3D-printed refillable drug delivery system (DDS) that fits the curvature of the eyeball. This DDS has three parts: a drug injection port for drug reloading, a drug release port with an opening for unidirectional release into the sclera, and a drug tank for drug retention. We evaluated in vitro the sustained release of fluorescein isothiocyanate conjugate (FITC)-albumin used as a model drug from 20 wt% poly(vinyl alcohol) (PVA) hydrogel placed at the release port over 200 days. Furthermore, we showed that ten successive drug refills could be carried out without problems. Finally, a smaller version of the DDS was implanted in vivo in rabbit sclera, which showed sufficient fluorescence release in the retina and the choroid/RPE homogenate. The present DDS with drug reloading capacity shows excellent promise as a minimally invasive drug administration tool for the long-term treatment of retinal diseases.