Representative confocal images of lymph nodes sections 6 h after periocular administration of 20 nm nanoparticles

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> Lymphatic circulation plays a role in the clearance of nanoparticles (20 nm) after periocular administration. Representative confocal images of lymph nodes sections, 6 h post periocular administration of 20 nm nanoparticles. Nanoparticles (20 nm; green) were administered to SD rats, live (Panels , , and ) and dead (Panels , , and ) by periocular injection. Lymph nodes, namely, cervical (Panels -), axillary (Panels -), and mesenteric (Panels -), were analyzed for the presence of nanoparticles by confocal microscopy. Lymph nodes of undosed SD rats were treated as controls (Panels , , and ). Green fluorescence associated with nanoparticles was observed in lymph node sections of live, but not dead, SD rats 6 h post periocular administration of nanoparticles. This suggests that in live animals lymphatic drainage delivered nanoparticles to various lymph nodes, however in dead rats, which are devoid viable lymphatic system, nanoparticles could not be detected in lymph nodes

Confocal images of the sclera-choroid-RPE combination at the end of 24 h nanoparticle (20 nm) transport study

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> Panel shows the fluorescence image and Panel shows the combination (fluorescence plus phase contrast) image of the control sclera-choroid-RPE tissue. Panel shows the fluorescence and Panel shows the combination (fluorescence plus phase contrast) image of the sclera-choroid-RPE tissue that was exposed to nanoparticles during the transport study. In each panel, the scleral (donor) side is on the left and the vitreal (receiver) side is on the right. The particles are concentrated on the outer edge of the sclera. There are very few or no particles seen on the vitreal side of the tissue

Representative confocal micrographs of various tissues 6 h after periocular administration of 20 nm particles

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> Following periocular administration of 400 µg dose of 20 nm particles to live rats, the nanoparticles can be found in the organs of the reticulo-endothelial system (liver and spleen). The various tissues including the eye, the periocular tissue, the liver and the spleen were removed and sectioned 6 h after administration. The figure shows the fluorescence images of sections of the: eye (Panels and ); periocular tissue (Panels and ); liver (Panels and ); and spleen (Panels and ). The left panels (, , , and ) are fluorescence images from control rats that were not dosed with the nanoparticles whereas the right panels (, , , and ) are images from the rats that were dosed with the nanoparticles. Nanoaprticles can be seen in the periocular tissue, spleen and to some extent in the liver of the dosed animals

Pharmacokinetic modeling of the disposition of 20 nm particles in the periocular space

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> Nanoparticle (20 nm) elimination from the periocular tissue is biphasic. The solid line represents the model predicted data while the circles represent the observed data. T and T represent half-lives for elimination from the periocular space. R: regression coefficient for the correlation between observed and predicted data

Dynamic barriers prevent significant entry of 20 nm particles into ocular tissues in live animals

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> Following periocular administration of 400 µg dose of 20 nm particles to either live (blood and lymphatic circulation present) or dead rats (blood and lymphatic circulation absent) the particle levels in the ocular tissues were quantified. Higher levels of the particles are seen in the sclera-choroid, retina, vitreous, and the cornea of dead rats as compared to live rats. The data are expressed as mean ± SEM for n=4

Sustained retinal delivery of a model drug (celecoxib) from nanoparticles with different clearance rates and drug release rates

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> The profiles were simulated for 20 nm and 200 nm particles for a period of 60 days. The elimination rate of the 20 nm formulation was obtained by curve fitting to the previously published data []. The estimated elimination half-life for 20 nm particles was 5.5 h. The elimination half-life for the 200 nm particles was assumed to be 180 days since they persisted almost completely for at least two months in the periocular space []. All other model parameters used in the model are shown in . The structural model is shown above the simulation. The panels depict profiles of 20 and 200 nm particles with a release rate constant of 0.016 min (), profiles of 20 and 200 nm particles with a release rate constant of 0.0016 min(), profiles of 20 and 200 nm particles with a release rate constant of 0.00016 min (), and profiles of 20 and 200 nm particles with a release rate constant of 0.000016 min (). The insets in each panel are the profiles for the first 24 h of drug release to better show the early differences between the retinal concentrations of celecoxib using 20 and 200 nm particles

Confocal images of the sclera at the end of the 24 h nanoparticle (20 nm) transport study

<p><b>Copyright information:</b></p><p>Taken from "Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration"</p><p></p><p>Molecular Vision 2008;14():150-160.</p><p>Published online 29 Jan 2008</p><p>PMCID:PMC2254958.</p><p></p> shows the control fluorescence and combined fluorescence while shows the phase contrast images. and are nanoparticle exposed tissue fluorescence and combined fluorescence and phase contrast images, respectively. In each image, the scleral (donor) side is on the left and the vitreal (receiver) side is on the right. The particles are concentrated on the outer edge of the sclera. There are very few or no particles on the vitreal side of the tissue