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Bryce Chiang, Mark R Prausnitz; Distribution and Clearance of Particles and Molecules after Microneedle Injection into the Suprachoroidal Space. Invest. Ophthalmol. Vis. Sci. 2016;57(12):761.
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© ARVO (1962-2015); The Authors (2016-present)
Microneedle injection into the suprachoroidal space (SCS) enables highly targeted drug delivery to the choroid/retina with a procedure similar to an intravitreal injection. Previous studies demonstrated fast clearance of molecules from the SCS. We studied parameters that affect distribution and clearance of molecules and particles injected into the rabbit SCS.
A microneedle was used to inject fluid into the rabbit SCS ex vivo (N=4 per group). The fluid injected (25-150 µL) contained red fluorescent particles and fluorescein in Hank’s Balanced Salt Solution (HBSS). Image analysis was performed to find the distribution of particles and molecules.A microneedle was used to inject 50 µL of fluid into the rabbit SCS in vivo (N=4 per group). The fluid contained red fluorescent particles and [a] fluorescein in Hank’s Balanced Salt Solution (HBSS), [b] fluorescein isothiocyante (FITC-) labeled carboxymethyl cellulose (CMC) in HBSS, or [c] FITC-hyaluronic acid/chondroitin sulfate (HA/CS) in HBSS. Fluorescent fundus imaging was acquired noninvasively for up to 1 mo. Image analysis was performed to find the distribution of particles and molecules over time.
As the injection volume was increased from 25-150 µL, the area of particle and fluorescein coverage both increased linearly (r2=0.58). The area of particle coverage was significantly less than the fluorescein (p<0.0001) suggesting particle entrapment. The thickness of the expanded SCS was constant for all injection volumes (p=0.33).In eyes injected with formulation [a], the particles distribution was constant from 3 min post-injection to 1 mo. Initially the fluorescein occupied a larger area than the particles but was cleared by 2 d (p<0.0001). In eyes injected with formulation [b] and [c], particle and FITC-CMC or HA/CS increased in area together until clearance of the polymer (p=0.077). FITC-HA/CS cleared by 14 d (p<0.0001), and FITC-CMC cleared by 21 d (p<0.0001).
After injection into the rabbit SCS, molecules spread over a larger area than particles. The area of spread increased with increasing volume injected, but thickness of the expanded SCS remained constant. Injection of particles in viscous polymeric formulations led to initial localization of particles near the site of injection, followed by spreading of polymer and particles together, until the polymer was cleared from the SCS after 2-3 weeks.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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