Abstract
Purpose :
A major challenge in the treatment of retinal eye diseases is the delivery of therapeutic agents to the target site. Traditional intravitreal injection is based on the random, passive diffusion of molecules. Topical drug delivery to the retina is an even more complex challenge. The major hurdle for all medication or drug delivery systems is the narrow macromolecular matrix of the different ocular tissues, which act as a barrier and prevent the penetration of particles and drugs. In order to address specific cells or layers of the retina, the use of micro- or nanoparticles from biomaterial research promises targeted, biocompatible and safer applications. Previously published nanopropellers (NPs) that can be actively controlled through the vitreous body to reach the retina present a chance to reach desired targets in the retina. The propulsion takes place through the spiral shape of the magnetic NPs.
Methods :
In the present study, the biocompatibility and degradability of the NPs were adjusted by using different chemical materials. The biocompatibility was evaluated with several ocular cells and cell lines, including primary porcine Müller and RPE cells as well as the 661W, Mio-M1, and ARPE-19 cell line. The changes in the chemical composition of the NPs demand a revaluation of the delivery properties. To this end, the magnetic NP function was assessed with the prior mentioned primary cells and cell lines, porcine retinal organ cultures, and eyes. To investigate the propulsion of the NPs, they were labeled with fluorescent agents for imaging and analyzed with confocal microscopy in vitro, ex vivo, and after histological preparation.
Results :
Our studies on retinal cells and retinal organ cultures resulted in excellent biocompatibility of the NPs. Furthermore, since the NPs were now formed out of different degradable materials, the time of degradation could be customized. The still-intact propulsion properties were confirmed with OCT and confocal microscopy. The NPs could be controlled to and into the retina or retinal cells. Histological examinations confirmed that only the magnetic NPs arrived at the region of interest.
Conclusions :
The biodegradability and the active navigation of the nanopropellers to aimed positions in the retina promise new possibilities for targeted forms of delivery and therapy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.