Magnetically Controlled Intraocular Delivery of Dexamethasone Using Silica-Coated Magnetic Nanoparticles

Abstract

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina.

Figure 1

Intraocular drug delivery strategy and fundamental characterization of silica-coated magnetic nanoparticles (MNPs). (a) Schematic images showing drug delivery strategy used in this study (not to scale). (b) Dynamic light scattering data showing the size distribution of particles at each step. SMNPs, silica-coated magnetic nanoparticles; SMNPs-COOH, carboxylic acid-functionalized silica-coated MNPs. (c) Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) micrographs of silica-coated magnetic nanoparticles. (d, e) Biocompatibility of SMNPs determined from ATP content and LIVE/DEAD images, respectively. *p < 0.05; ns, not significant. n = 4.

Figure 2

Dexamethasone loading on SMNPs. (a) Stepwise dexamethasone loading on SMNPs. (b) Confirmation of dexamethasone loading by Fourier-transform infrared spectroscopy. (c) Vibrating sample magnetometry data before and after dexamethasone loading.

Figure 3

Release of dexamethasone from Dex@SMNPs. (a) Concentration of dexamethasone released from Dex@SMNPs dispersed in PBS (n = 3). (b) Viability of cells cocultured with SMNPs and Dex@SMNPs for 24 h, determined by measuring ATP content. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ns, not significant; n = 4. (c) LIVE/DEAD cell images of cells cocultured with Dex@SMNP for 24 h.

Figure 4

Magnetic manipulation of Dex@SMNPs within vitreous humor. (a) Magnetic actuation in vitreous humor of bovine eyes obtained within 2 days after slaughter (ex vivo). (b) Magnetic attraction of Dex@SMNPs inside vitreous humor of living New Zealand white rabbits (in vivo) under unidirectional and bidirectional movement conditions.