Abstract
Minor changes in the composition of poloxamer 188-modified, DEAE-dextran-stabilized (PDD) polybutylcyanoacrylate (PBCA) nanoparticles (NPs), by altering the physicochemical parameters (such as size or surface charge), can substantially influence their delivery kinetics across the blood-retina barrier (BRB) in vivo. We now investigated the physicochemical mechanisms underlying these different behaviors of NP variations at biological barriers and their influence on the cellular and body distribution. Retinal whole mounts from rats injected in vivo with fluorescent PBCA NPs were processed for retina imaging ex vivo to obtain a detailed distribution of NPs with cellular resolution in retinal tissue. In line with previous in vivo imaging results, NPs with a larger size and medium surface charge accumulated more readily in brain tissue, and they could be more easily detected in retinal ganglion cells (RGCs), demonstrating the potential of these NPs for drug delivery into neurons. The biodistribution of the NPs revealed a higher accumulation of small-sized NPs in peripheral organs, which may reduce the passage of these particles into brain tissue via a "steal effect" mechanism. Thus, systemic interactions significantly determine the potential of NPs to deliver markers or drugs to the central nervous system (CNS). In this way, minor changes of NPs' physicochemical parameters can significantly impact their rate of brain/body biodistribution.
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