Search

The potential of poly(lactic-co-glycolic acid) (PLGA) to design nanoparticles (NPs) and target the central nervous system remains to be exploited. In the current study we designed fluorescent 70-nm PLGA NPs, loaded with bulky fluorophores, thereby making them significantly brighter than quantum dots in single-particle fluorescence measurements. The high brightness of NPs enabled their visualization by intravital real-time 2-photon microscopy. Subsequently, we found that PLGA NPs coated with pluronic F-68 circulated in the blood substantially longer than uncoated NPs and were taken up by cerebro-vascular endothelial cells. Additionally, confocal microscopy revealed that coated PLGA NPs were present in late endothelial endosomes of cerebral vessels within 1 h after systemic injection and were more readily taken up by endothelial cells in peripheral organs. The combination of ultra-bright NPs and in vivo imaging may thus represent a promising approach to reduce the gap between development and clinical application of nanoparticle-based drug carriers. We designed highly fluorescent poly(lactic-co-glycolic acid) nanoparticles, loading them by bulky dye molecules. This allowed us to examine in vivo how coating by Pluronic F68 influences nanoparticles biodistribution, emphasizing brain distribution. We subsequently found that Pluronic F68 relocates particles from macrophages into endothelial cells, specifically in late endosomes. [Display omitted] [ABSTRACT FROM AUTHOR]