How Nanoparticle Physicochemical Parameters Affect Drug Delivery to Cells in the Retina via Systemic Interactions

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.

Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases

“…82 Various kinds of polybutylcyanoacrylate (PBCA) NPs were delivered in mice via IVI. 83,84 Middle-sized PBCA NPs (272 nm) with ζ = 5 mV resulted in a highly efficient BRB passage but did not open the BRB, while PBCA NPs of reduced size ( d = 172 nm) showed reduced passage, 85 as confirmed by in vivo confocal neuroimaging (ICON). The difference is believed to be due to the different uptake mechanism, with particles below 200 nm in diameter being taken up through clathrin-mediated endocytosis, whereas larger particles up to a size of 500 nm utilize caveolae-mediated uptake.…”

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment

“…The effects of the nanoparticles’ size and zeta potential on their capability to trespass the biological barriers were also studied, showing that larger PBCA NPs (272 versus 172 nm) with intermediate z potential (5 V versus 0 V and 15 V) were more likely to concentrate in the retina. Their accumulation in RGCs, together with their well-documented safety profile in humans, makes this polymer a viable option for delivering retinal therapies [ 89 , 90 ].…”

Nanomedicine and drug delivery to the retina: current status and implications for gene therapy

“…In sum, PBCA NPs with a larger size and medium surface charge were more likely to accumulate in retinal tissue. As they are easily detected in RGCs, the NPs have an excellent potential to serve as a retinal drug delivery system, and they have a good and well-characterized safety profile in patient studies (You et al 2019a(You et al , 2019b.…”