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

Shirin Tavakoli, Otto Kalevi Kari, Tiina Turunen, Tatu Lajunen, Mechthild Schmitt, Julia Lehtinen, Fumitaka Tasaka, Petteri Parkkila, Joseph Ndika, Tapani Viitala, Harri Alenius, Arto Urtti, Astrid Subrizi*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)699-713
Number of pages15
JournalMolecular Pharmaceutics
Volume18
Issue number2
DOIs
Publication statusPublished - 1 Feb 2021
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Keywords

  • lipid-based nanoparticle
  • ocular pharmacokinetics
  • protein corona
  • proteomics
  • single-particle tracking
  • vitreal diffusion

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