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Personne :
Bertrand, Nicolas

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Bertrand

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Nicolas

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Université Laval. Faculté de pharmacie

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ncf11899258

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  • PublicationAccès libre
    Anti-polyethylene glycol antibodies alter the protein corona deposited on nanoparticles and the physiological pathways regulating their fate in vivo
    (Elsevier, 2018-10-10) Grenier, Philippe; Oliveira Viana, Iara Maíra de; Lima, Eliana Martins; Bertrand, Nicolas
    Multiple studies highlight the strong prevalence of anti-poly(ethylene glycol) (anti-PEG) antibodies in the general human population. As we develop therapeutic modalities using this polymer, it is increasingly relevant to assess the importance of anti-PEG antibodies on biological performances. Here, we show that the anti-PEG Immunoglobulin M (IgM) raised in mice following the injection of polymeric nanoparticles could have significant neutralizing effects on subsequent doses of PEGylated nanosystems in vivo. The circulation times of PEGylated nanoparticles and liposomes were strongly reduced in animals with circulating anti-PEG IgMs, irrespective of the PEG density or the surface properties of the system. In comparison, despite that anti-PEG IgMs could bind free methoxy-terminated PEG and PEGylated bovine serum albumin, the circulation kinetics of these systems remained unaltered in the presence of antibodies. The binding of IgMs to the PEGylated surface of nanoparticles alters the nature of the proteins adsorbed in the surrounding corona, notably due to the activation of the complement cascade. These changes are responsible for the observed differences in circulation times. In comparison, the PEG-BSA is unable to activate complement, even in the presence of anti-PEG IgMs. These results inform on how anti-PEG antibodies can affect the fate of PEGylated nanomaterials and highlight how the architecture of nanoparticles impacts the deposition of the protein corona.
  • PublicationRestreint
    Drinkable lecithin nanovesicles to study the biological effects of individual hydrophobic macronutrients and food preferences
    (Elsevier, 2020-04-07) Chotard, Élodie; Mohammadi, Farzad; Rudkowska, Iwona; Bertrand, Nicolas; Berthiaume, Line; Julien, Pierre
    Fundamental nutritional studies on bioactive molecules require minimizing exposure to confounding foreign elements, like solvents. Herein, aqueous formulations of lecithin nanovesicles are proposed to study three individual trans fatty acids relevant to human nutrition: elaidic acid, trans-vaccenic acid and trans-palmitoleic acid. This proof-of-concept study describes the encapsulation of fatty acids, in vivo bioavailability, and the use of nanovesicles in behavioral experiments. The oral bioavailability of the encapsulated molecules and the selective exposure of animals to each trans-fatty acid of interest were confirmed in healthy rats. Behavioral studies also evidenced that nanovesicles can be used to evaluate the palatability of the lipids and investigate food preferences in mice. Altogether this study shows that lecithin nanovesicles offer an elegant tool to efficiently deliver hydrophobic molecules to animal models. This approach paves the way for future studies deconvoluting the nutritional effects of trans-fatty acids.
  • PublicationAccès libre
    Residual solvents in nanomedicine and lipid-based drug delivery systems : a case study to better understand processes
    (Springer, 2020-07-17) Dikpati, Amrita; Queant, Caroline; Mohammadi, Farzad; Rudkowska, Iwona; Greffard, Karine; Bertrand, Nicolas; Arnaud, Philippe; Bastiat, Guillaume
    Purpose : Complexities surrounding the manufacture and quality control of nanomedicines become increasingly apparent. This research article offers a case study to investigate how, at the laboratory scale, various stages of liposome and nanoparticle synthesis affect the amount of residual solvent found in the formulations. The objective is to bring insights on the reliability of each of these processes to provide final products which meet regulatory standards and facilitate identifying possible bottleneck early during the development process. Methods : The residual solvent at various stages of preparation and purification was measured by headspace gas chromatography. Liposomes were prepared by two different methods with and without solvent. Polymer nanoparticles prepared via nanoprecipitation and purified by ultrafiltration were studied. The effects of purification by size exclusion chromatography and dialysis were also investigated. Results : The complete removal of residual solvent requires processes which go beyond usual preparation methods. Conclusions : This work might prove valuable as a reference for scientists of different fields to compare their own practices and streamline the translation of nanomedicines into efficacious and safe drug products.