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Yoo Kim, Mark Prausnitz, Henry Edelhauser; Distribution And Clearance Of Microparticles And Nanoparticles In The Suprachoroidal Space After Injection Using Hollow Microneedles In Rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1098.
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The suprachoroidal space (SCS) is a virtual space between the sclera and choroid tissues and has been shown to accommodate a variety of fluids and particles in rabbit and porcine eyes. Drugs delivered in this potential space can be used to treat posterior-segment diseases such as age-related macular degeneration. This study examines the distribution and clearance of microparticles and nanoparticles after administration within the SCS using a hollow microneedle up to 112 days following injection into eyes of New Zealand White rabbit eyes.
Hollow metal microneedles 750-800 µm in length were used to inject 50 µL of non-biodegradable, fluorescently tagged, polystyrene particles with various sizes (20 nm, 200 nm, 2 µm, 10 µm) in balanced salt solution. A hollow microneedle was inserted 3 mm posterior to the limbus in New Zealand White rabbit eyes. Rabbits were sacrificed 14 or 112 days after injection. The eyes were snap frozen, dissected and imaged to visualize the spread of the particles within the SCS followed by a homogenization process to quantify the number of particles inside the SCS by fluorescence.
Fourteen days after injection, the 20 nm, 200 nm, 2 µm and 10 µm sized particles covered an suprachoroidal surface area of 201±44 mm2, 191±25 mm2, 169±19 mm2 and 185±10 mm2, respectively. After 112 days, these particles covered an area of 131±4.7 mm2, 135±1.3 mm2, 127±24 mm2 and 170±11 mm2, respectively. These particles showed a 35%, 30%, 25%, and 9% reduction in coverage area, respectively between days 14 and 112, which was statistically significant (p < 0.001). In addition, the number of particles decreased between days 14 and 112, as shown by a 48%, 69%, 45% and 28% reduction in fluorescent signal intensity of particles, which was statistically significant (p < 0.001).
A single hollow microneedle was able to reliably inject 50 µL of particle formulations that have a particle size up to 10 µm within the SCS of rabbit eyes. The particles spread over a suprachoroidal area of up to 200 mm2, which decreased by 9 - 35% between days 14 and 112. In addition, 28% - 69% of the particles appeared to be cleared from the SCS between days 14 and 112. We are currently determining whether this apparent clearance is due to removal by macrophages or simply a reduction of the fluorescence signal intensity of the particles over time.
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