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

[Image: see text] 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 plasmo...

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Autores principales: Tavakoli, Shirin, Kari, Otto Kalevi, Turunen, Tiina, Lajunen, Tatu, Schmitt, Mechthild, Lehtinen, Julia, Tasaka, Fumitaka, Parkkila, Petteri, Ndika, Joseph, Viitala, Tapani, Alenius, Harri, Urtti, Arto, Subrizi, Astrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856631/
https://www.ncbi.nlm.nih.gov/pubmed/32584047
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00411
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author Tavakoli, Shirin
Kari, Otto Kalevi
Turunen, Tiina
Lajunen, Tatu
Schmitt, Mechthild
Lehtinen, Julia
Tasaka, Fumitaka
Parkkila, Petteri
Ndika, Joseph
Viitala, Tapani
Alenius, Harri
Urtti, Arto
Subrizi, Astrid
author_facet Tavakoli, Shirin
Kari, Otto Kalevi
Turunen, Tiina
Lajunen, Tatu
Schmitt, Mechthild
Lehtinen, Julia
Tasaka, Fumitaka
Parkkila, Petteri
Ndika, Joseph
Viitala, Tapani
Alenius, Harri
Urtti, Arto
Subrizi, Astrid
author_sort Tavakoli, Shirin
collection PubMed
description [Image: see text] 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.
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spelling pubmed-78566312021-02-03 Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations Tavakoli, Shirin Kari, Otto Kalevi Turunen, Tiina Lajunen, Tatu Schmitt, Mechthild Lehtinen, Julia Tasaka, Fumitaka Parkkila, Petteri Ndika, Joseph Viitala, Tapani Alenius, Harri Urtti, Arto Subrizi, Astrid Mol Pharm [Image: see text] 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. American Chemical Society 2020-06-25 2021-02-01 /pmc/articles/PMC7856631/ /pubmed/32584047 http://dx.doi.org/10.1021/acs.molpharmaceut.0c00411 Text en This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Tavakoli, Shirin
Kari, Otto Kalevi
Turunen, Tiina
Lajunen, Tatu
Schmitt, Mechthild
Lehtinen, Julia
Tasaka, Fumitaka
Parkkila, Petteri
Ndika, Joseph
Viitala, Tapani
Alenius, Harri
Urtti, Arto
Subrizi, Astrid
Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title_full Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title_fullStr Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title_full_unstemmed Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title_short Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations
title_sort diffusion and protein corona formation of lipid-based nanoparticles in the vitreous humor: profiling and pharmacokinetic considerations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856631/
https://www.ncbi.nlm.nih.gov/pubmed/32584047
http://dx.doi.org/10.1021/acs.molpharmaceut.0c00411
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