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Lipid Coating of Chitosan Nanogels for Improved Colloidal Stability and In Vitro Biocompatibility

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Abstract

Chitosan-based carriers have coined their position as delivery agents. When assembled with polyanions into nanogels (NG), these vectors have enabled the delivery of drugs, genes, and proteins to a myriad of applications. However, the chemical and colloidal instability of chitosan nanoformulations in physiologically compatible media prejudices in vitro biocompatibility and, thus, scale-up applications. To overcome this issue, we envisaged the coating of chitosan nanogel with phospholipids. In this investigation, we report a two-stage synthesis of hybrid lipid-coated chitosan nanogels, named nanolipogels (NLG), to improve colloidal stability and in vitro biocompatibility over chitosan NG. Practically, we employed a mixing platform to first prepare chitosan NG by ionic gelation, dilute the suspension, and, in a second stage, coat the NG with lipids. We demonstrate that lipid coating increased particle size and reversed the ζ-potential to negative values, suggesting the successful formation of NLG, while maintaining a homogeneous size distribution (PDI < 0.25). Furthermore, multiple light scattering analysis confirmed NLG improved colloidal stability in phosphate buffer saline and cell culture medium, with respect to NG. Finally, lipid coating completely abrogated the cytotoxicity of NG when incubated at 50 μg·mL−1 with HeLa, U87, or b.End3 cell lines and significantly improved the biocompatibility at 100 and 150 μg·mL−1. Future investigations will explore how the lipid coating affects drug loading, release profile, and the ability of NLG to deliver drugs and genes in vitro.

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Acknowledgements

The authors acknowledge financial support from National Sciences and Engineering Research Council (JLC grant # RGPIN-2018-05682; VGR grant # RGPIN/06636-2018). The MLS Nanobrook Omni DLS and TurbiscanLAB™ used in this study were acquired with funds from Canada Foundation for Innovation (VGR grant # #34227). VPG acknowledges the support of Mitacs Inc. (Mitacs Globalink Graduate Fellowship Award GLF407).

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Authors and Affiliations

  1. Faculty of Pharmacy, Université de Montréal, Montréal, Québec, H3C 3J7, Canada

    Victor Passos Gibson, Julia Balestrero Braga Nunes, Deborah Quintanilha Falcao, V. Gaëlle Roullin & Jeanne Leblond Chain

  2. Programa de Pós-Graduação em Ciências Aplicadas a Produtos para Saúde, Faculdade de Farmácia, Universidade Federal Fluminense, Rua Doutor Mário Viana 523, Santa Rosa, Niterói, 24241-000, Brazil

    Deborah Quintanilha Falcao

  3. Université de Bordeaux, CNRS, INSERM, ARNA, UMR 5320, U1212, F-33000, Bordeaux, France

    Jeanne Leblond Chain

Authors
  1. Victor Passos Gibson
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  2. Julia Balestrero Braga Nunes
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  3. Deborah Quintanilha Falcao
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  4. V. Gaëlle Roullin
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  5. Jeanne Leblond Chain
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Contributions

Victor Passos Gibson: methodology, formal analysis, investigation, writing — original draft, and writing — review & editing; Julia Balestrero Braga Nunes: investigation; Deborah Quintanilha Falcão: conceptualization, methodology, and investigation; V. Gaëlle Roullin: conceptualization, resources, writing — review & editing, funding acquisition, and supervision; Jeanne Leblond Chain: conceptualization, resources, writing — review & editing, funding acquisition, and supervision.

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Correspondence to Jeanne Leblond Chain.

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Supplementary Information

Supplemental Information includes 1 table and 3 figures, the detailed materials and method section, as well as the data available in this study.

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Passos Gibson, V., Nunes, J.B.B., Falcao, D.Q. et al. Lipid Coating of Chitosan Nanogels for Improved Colloidal Stability and In Vitro Biocompatibility. AAPS PharmSciTech 22, 159 (2021). https://doi.org/10.1208/s12249-021-02027-5

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  • DOI: https://doi.org/10.1208/s12249-021-02027-5

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