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

doi:10.1021/acs.molpharmaceut.0c00411

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 journal › Article › Scientific › peer-review

49 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 language	English
Pages (from-to)	699-713
Number of pages	15
Journal	Molecular Pharmaceutics
Volume	18
Issue number	2
DOIs	https://doi.org/10.1021/acs.molpharmaceut.0c00411
Publication status	Published - 1 Feb 2021
Externally published	Yes
MoE publication type	A1 Journal article-refereed

Funding

S.T., an early stage researcher within the NANOMED project, acknowledges the funding received from the European Union’s Horizon 2020 research and innovation program Marie Skłodowska-Curie Innovative Training Networks (ITN) (grant 676137). SPR and proteomics studies were funded through grants from the Instrumentarium Science Foundation, Inkeri and Mauri Vänskä Foundation, and Drug Research Program Joint Grant. A.S. received support from the Lundbeck Foundation (grant R181-2014-3577) and A.U. from the Academy of Finland (grant 311122). The authors also acknowledge the funding received from Santen Oy. The Light Microscopy Unit of the Institute of Biotechnology at the University of Helsinki is thanked for help with confocal microscopy. M.Sc. Marja Hagström is thanked for assistance in proteomics sample preparation.

Keywords

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

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10.1021/acs.molpharmaceut.0c00411

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Tavakoli, S., Kari, O. K., Turunen, T., Lajunen, T., Schmitt, M., Lehtinen, J., Tasaka, F., Parkkila, P., Ndika, J., Viitala, T., Alenius, H., Urtti, A., & Subrizi, A. (2021). Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations. Molecular Pharmaceutics, 18(2), 699-713. https://doi.org/10.1021/acs.molpharmaceut.0c00411

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

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.",

keywords = "lipid-based nanoparticle, ocular pharmacokinetics, protein corona, proteomics, single-particle tracking, vitreal diffusion",

author = "Shirin Tavakoli and Kari, \{Otto Kalevi\} and Tiina Turunen and Tatu Lajunen and Mechthild Schmitt and Julia Lehtinen and Fumitaka Tasaka and Petteri Parkkila and Joseph Ndika and Tapani Viitala and Harri Alenius and Arto Urtti and Astrid Subrizi",

note = "Funding Information: S.T., an early stage researcher within the NANOMED project, acknowledges the funding received from the European Union{\textquoteright}s Horizon 2020 research and innovation program Marie Sk{\l}odowska-Curie Innovative Training Networks (ITN) (grant 676137). SPR and proteomics studies were funded through grants from the Instrumentarium Science Foundation, Inkeri and Mauri V{\"a}nsk{\"a} Foundation, and Drug Research Program Joint Grant. A.S. received support from the Lundbeck Foundation (grant R181-2014-3577) and A.U. from the Academy of Finland (grant 311122). The authors also acknowledge the funding received from Santen Oy. The Light Microscopy Unit of the Institute of Biotechnology at the University of Helsinki is thanked for help with confocal microscopy. M.Sc. Marja Hagstr{\"o}m is thanked for assistance in proteomics sample preparation. Publisher Copyright: {\textcopyright} 2021 American Chemical Society. All rights reserved.",

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Tavakoli, S, Kari, OK, Turunen, T, Lajunen, T, Schmitt, M, Lehtinen, J, Tasaka, F, Parkkila, P, Ndika, J, Viitala, T, Alenius, H, Urtti, A & Subrizi, A 2021, 'Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations', Molecular Pharmaceutics, vol. 18, no. 2, pp. 699-713. https://doi.org/10.1021/acs.molpharmaceut.0c00411

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AU - Tavakoli, Shirin

AU - Kari, Otto Kalevi

AU - Turunen, Tiina

AU - Lajunen, Tatu

AU - Schmitt, Mechthild

AU - Lehtinen, Julia

AU - Tasaka, Fumitaka

AU - Parkkila, Petteri

AU - Ndika, Joseph

AU - Viitala, Tapani

AU - Alenius, Harri

AU - Urtti, Arto

AU - Subrizi, Astrid

N1 - Funding Information: S.T., an early stage researcher within the NANOMED project, acknowledges the funding received from the European Union’s Horizon 2020 research and innovation program Marie Skłodowska-Curie Innovative Training Networks (ITN) (grant 676137). SPR and proteomics studies were funded through grants from the Instrumentarium Science Foundation, Inkeri and Mauri Vänskä Foundation, and Drug Research Program Joint Grant. A.S. received support from the Lundbeck Foundation (grant R181-2014-3577) and A.U. from the Academy of Finland (grant 311122). The authors also acknowledge the funding received from Santen Oy. The Light Microscopy Unit of the Institute of Biotechnology at the University of Helsinki is thanked for help with confocal microscopy. M.Sc. Marja Hagström is thanked for assistance in proteomics sample preparation. Publisher Copyright: © 2021 American Chemical Society. All rights reserved.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - 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.

AB - 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.

KW - lipid-based nanoparticle

KW - ocular pharmacokinetics

KW - protein corona

KW - proteomics

KW - single-particle tracking

KW - vitreal diffusion

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DO - 10.1021/acs.molpharmaceut.0c00411

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SN - 1543-8384

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ER -

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

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