Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations

The
vitreous humor is the first barrier encountered by intravitreally
injected nanoparticles. Lipid-based nanoparticles in the vitreous
are studied by evaluating their diffusion with single-particle tracking
technology and by characterizing their protein coronae with surface
plasmon resonance and high-resolution proteomics. Single-particle
tracking results indicate that the vitreal mobility of the formulations
is dependent on their charge. Anionic and neutral formulations are
mobile, whereas larger (>200 nm) neutral particles have restricted
diffusion, and cationic particles are immobilized in the vitreous.
PEGylation increases the mobility of cationic and larger neutral formulations
but does not affect anionic and smaller neutral particles. Convection
has a significant role in the pharmacokinetics of nanoparticles, whereas
diffusion drives the transport of antibodies. Surface plasmon resonance
studies determine that the vitreal corona of anionic formulations
is sparse. Proteomics data reveals 76 differentially abundant proteins,
whose enrichment is specific to either the hard or the soft corona.
PEGylation does not affect protein enrichment. This suggests that
protein-specific rather than formulation-specific factors are drivers
of protein adsorption on nanoparticles in the vitreous. In summary,
our findings contribute to understanding the pharmacokinetics of nanoparticles
in the vitreous and help advance the development of nanoparticle-based
treatments for eye diseases.