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In vivo visualization different kinetic of active compound encapsulated in PLGA nanoparticles at the blood-retinal barrier
Enqi Zhang
US Food and Drug administration (FDA) approved product poly (lactic-co-glycolic acid) nanoparticles (PLGA NP) have a huge potential as drug delivery systems, for imaging and diagnostic methods. Here, with In vivo Confocal Neuroimaging (ICON) we visualize in real time the biodistribution of fluorescent nanoparticles in vessels of the retina by microscopic evaluation of the distribution of the fluorescence. When working with Rhodamine123 (Rho123) labelled PLGA NPs we observed disappearance of the fluorescence within the first 15 minutes after injection. However, with 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI) labelled poly (lactic-co-glycolic acid) nanoparticles showed more long-lasting e ects. The final result showed that fluorescent signal of the hydrophobic marker DiI can last for more than 1.5 hours in blood vessels which are significantly longer than for the hydrophilic Rho123, although Rho123 as well as DiI-labelled PLGA NP were clearly visible a significant fluorescent signal in the retina vessels from shortly after injection up to approximately 5 min later. In the case of Rho123-labelled PLGA NP application, no fluorescent was detectable at later time-points 15 min, but clearly visible fluorescent lining of the vessels can be seen for more than 2 hours after injection of DiI-loaded PLGA NP. By quantification of the fluorescent signal in the retina blood vessel we created a temporal-spatial map of the active ingredients distribution. With this work we contribute to a better understanding of the causal relationship between design of nanoparticulate carrier systems and their distribution at the blood-retinal barrier (BRB), which will be helpful for future drug development projects for the treatment of optic nerve damage, for example after glaucoma or optic neuropathy.

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