PHOTODOCTOR · Photodynamic Ocular Drug Delivery System with Optical Coherence Tomography Oriented Microscale Robots

Photodynamic Ocular Drug Delivery System with Optical Coherence Tomography Oriented Microscale Robots

Retinal diseases are the most common reason for irreversible blindness worldwide. Common retinal diseases, such as diabetic retinopathy, macular degeneration, retinal vein occlusion, and non-infectious uveitis, mostly require intravitreal steroid injections in clinical management. Unfortunately, the intravitreal steroid injections lead to other critical ocular problems, such as elevation of intraocular pressure, intravitreal infections, and progression of cataracts. Because of these reasons, targeted drug delivery systems are necessary for the medical treatment of retinal diseases. Photodynamic Ocular Drug Delivery System with Optical Coherence Tomography Oriented Microscale Robots (PHOTODOCTOR) project combines three novel technologies to solve this significant clinical problem. The first technological advancement for the project is dexamethasone-saturated hyaluronic acid (HA) hydrogels with organo-ruthenium complexes, which enables controllable degradation under visible light exposure. With the help of visible light-controlled degradation, dexamethasone can be released with the light pulses. Then, the hydrogels are supplemented with superparamagnetic iron oxide nanoparticles (SPIONs) and 3D printed as helical small-scale swimmers. Insertion of the SPIONs helps the magnetic actuation of the hydrogel-based small-scale robots in the intraocular space. Lastly, SPION-supplemented HA hydrogels can be observed with a high-resolution optical coherence tomography (OCT) system in the intraocular space to guide them in diseased areas of the retina. While HA-based structures increase penetration in vitreous cells and help attachment to the retina, SPIONs increase the visibility of the small-scale robots in OCT imaging. In this way, a magnetic-driven, visible light-triggered intraocular drug release system with OCT guidance is produced, and it could be used not only for intravitreal steroid delivery but also for the treatment of retinal tumors and other retinal problems. In this project, we investigated several possibilities for hydrogel-based small-scale robots for intraocular drug delivery methods. We focused on the investigation of the possibilities for intraocular drug delivery with small-scale degradable robots in six main subjects: material selection, 3D-printing method, magnetic actuation, medical imaging, drug delivery, and biocompatibility. In each focused subject, we examined several possible state-of-the-art techniques to advance the current design of the intraocular implants and rebuild them as untethered actuable systems. After a detailed investigation of several possible systems, the current possible intraocular drug delivery system proposal is summarized in the graphical abstract. After several trials with various combinations, the most feasible, reproducible, and realistic small-scale hydrogel-based degradable robots for intraocular steroid delivery are produced with the digital light processing 3D printing method. We designed and fabricated magnetically controllable degradable milliscale swimmers as intraocular drug implants using magnetic nanoparticle decorated acrylated polyethylene glycol hydrogel precursors with digital light processing 3D printing method. The magnetically controllable hydrogel-based swimmers have comparable dimensions with commercial intraocular implants that achieve high velocities in both aqueous and vitreous humor environments. Thanks to their high drug delivery capacities and slow degradation profiles, they can release the medications without disrupting retinal epithelial viability and barrier function.

Data: CORDIS, © European Union