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A.C. Amrite, S.P. Ayalasomayajula, U.B. Kompella; Nano- and Micro-Particles Reach Retina Following Systemic but Not Subconjunctival Administration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4449.
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Purpose: To compare the ocular tissue distribution of non-degradable, fluorescent nano- and micro- particles following systemic and subconjunctival routes of administration. Methods: All studies were carried out in male Sprague Dawley rats. For the systemic studies, sodium fluorescein (4 mg), 2 µm particles (fluospheresTM, 200µg) or 20 nm particles (fluospheresTM, 200µg) were administered via intracardiac injection under sodium pentobarbital anesthesia. Fifteen minutes after dosing, the animals were sacrificed. For the subconjunctival studies, the animals received 400 µg of nano- or micro- particles via subconjunctival injection into one eye under anesthesia. Animals were sacrificed 1 or 7 days after treatment. After sacrifice, the eyes were enucleated, frozen and the lens, cornea, sclera-choroid, retina, and vitreous were isolated, extracted for intact particles, and the fluorescence was quantified. Results: Following systemic administration, nanogram quantities of sodium fluorescein, nanoparticles, and microparticles were detected in all tissues, with the statistically significant rank order of distribution being sclera-choroid>cornea=retina>vitreous>lens with the nanoparticles and cornea>retina>sclera-choroid>vitreous>lens with the microparticles. The dose-normalized mass accumulation was 40-150 folds higher with the micro- and nano- particles compared to sodium fluorescein, possibly due to the rapid clearance of sodium fluorescein from the ocular tissues. With subconjunctival nanoparticle administration, significant amount was detected only in the sclera-choroid at the end of 1 day in the ipsilateral eye, while the microparticles showed negligible penetration in all the ocular tissues. The micro- or nano- particles were not detected in the contralateral eye or the plasma at the end of 1 or 7 days. Although unlikely, the absorption and disappearance of particles from the ocular tissues within one day cannot be ruled out. Conclusions: Nano- and micro- particles can access the intraocular tissues through the systemic circulation, with the accumulation being much higher than sodium fluorescein. The subconjunctivally administered micro- and nano- particles failed to reach the intraocular tissues under the conditions of this study. If subconjunctivally administered particulate systems remain in the subconjunctival space, such systems can be used to sustain drug delivery to the intraocular tissues.
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