Protein corona formation on lipidic nanocapsules: Influence of the interfacial PEG repartition

The parameters currently used for characterization of nanoparticles, such as size and zeta potential, were not able to reflect the performance of a nanocarrier in the biological environment. Therefore, more thorough in vitro characterization is required to predict their behavior in vivo, where nanoparticles acquire a new biological identity due to interactions with biomolecules. In this present study, we performed in vitro characterization in biological fluids for lipid nanocapsules (LNCs) with varying means sizes (50 nm and 100 nm), different electrical surface charges and different Poly Ethylene Glycol (PEG) compositions. Then, different methods were applied to show the impact of the protein corona formation on LNCs.

Highlights

  • Modification of physicochemical characteristics of nanoparticles after plasmatic proteins incubation.
  • Non homogeneous PEG coverage increases proteins adsorption on 50-nm LNCs but not 100-nm LNCs.
  • Ohshima method can predict the corona protein nanoparticle formation.

Even if all formulations attached to plasmatic proteins, a higher thickness of corona and highest protein binding was observed for certain LNC50 formulations. A better knowledge of the phenomenon of protein adsorption over NPs in the plasmatic media is a cornerstone of clinical translation. In fact, after short blood circulation time, it is not the initially designed nanoparticle but the complex nanoparticle bearing its protein corona which circulates to reach its target.

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Materials

Dulbecco’s Phosphate Buffered Saline (PBS), octadecylamine (stearylamine), Bovine Serum Albumin (BSA), sodium chloride and potassium chloride were supplied by Sigma-Aldrich (Saint-Quentin-Fallavier, France). Kolliphor® HS-15 (PEG 660 and polyethylene glycol 660 hydroxystearate mixture) was purchased from BASF (Ludwigshafen, Germany). Lipoid® S75–3 (phosphatidylcholine and phosphatidylethanolamine mixture) were purchased from Lipoid GmbH (Steinhausen, Switzerland). Captex® 8000 (glyceryl tricaprylate) was kindly provided by Abitec Corporation (Columbus, OH, USA). DSPE-mPEG-2000 (1,2-distearoyl-sn‑glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)−2000] (ammonium salt)) was purchased Avanti Polar Lipids (Alabaster, AL, USA). Ultrapure water was obtained from a Milli-Q® Advantage A10 System (Merck Millipore, Darmstadt,

Vincent Lebreton, Samuel Legeay, Anastasiia Vasylaki, Fredéric Lagarce, Patrick Saulnier, Protein corona formation on lipidic nanocapsules: Influence of the interfacial PEG repartition, European Journal of Pharmaceutical Sciences,
Volume 189, 2023, 106537, ISSN 0928-0987, https://doi.org/10.1016/j.ejps.2023.106537.


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