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S. R. Patel, D. Berezovsky, B. E. McCarey, J. M. Nickerson, H. F. Edelhauser, M. R. Prausnitz; Intraocular Pharmacokinetics of Suprachoroidal Drug Delivery Administered Using Hollow Microneedles. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3796. doi: https://doi.org/.
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Posterior segment ocular drug delivery is dominated by strategies that poorly target the retinochoroidal space and are often invasive. Delivering to the suprachoroidal space (SCS), between the sclera and choroid, has been of recent interest because of its close proximity to the choroid and retina and its ability to hold fluid. However, methods of delivery have been invasive and the potential for sustained delivery has not been studied. We present here a minimally invasive delivery method using hollow microneedles that can locally target the SCS. The purpose of this study is to understand the distribution and kinetics of the clearance of compounds and particles from the SCS and compare to intravitreal (IV) delivery using flurophotometry.
Hollow glass microneedles were used to infuse fluorescein and 20- and 500-nm particle suspensions into the SCS by inserting them transsclerally. A pen-like device was made for SCS injection using a single microneedle. IV injections of fluorescein were performed with a 30g hypodermic needle. Experiments were performed in-vivo on New Zealand rabbits. An ocular flurophotometer was used to quantify concentrations in the whole eye in situ.
Fluorescein injections into the SCS were localized with high concentration in the SCS and many-fold lower levels in the vitreous. IV injections resulted in a fairly uniform concentration throughout the vitreous within 2 hours, which decreased over time. The half life for SCS and IV injection was 1.3 and 2.4 hours respectively. Nanoparticle suspensions were also injected into the SCS, which resulted in similar localization to the SCS, as seen for fluorescein. However, over time the nanoparticle concentrations maintained relatively constant levels in the SCS with minimal levels in the vitreous. At the four-week time point, most particles were still present and had not cleared from the SCS. Gross examination of the animals during the experiments revealed no ocular inflammation or irritation from the SCS injection.
We show here, for the first time, a minimally invasive method utilizing a microneedle to inject solutions and nanoparticle suspensions into the SCS in-vivo. SCS injections were capable of localizing the injected material in the posterior segment of the eye along the retinochoroidal surface. Nanoparticles had residence times of at least one month, which provides the potential for sustained delivery to the posterior segment.
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