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An injectable, nanostructured implant for the delivery of adenosine triphosphate: towards long-acting formulations of small, hydrophilic drugs.
Giacalone, Giovanna; Quaillet, Marion; Huang, Nicolas; Nicolas, Valérie; Boulogne, Claire; Gillet, Cynthia; Fattal, Elias; Bochot, Amélie; Hillaireau, Hervé.
Afiliação
  • Giacalone G; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, 91400, France.
  • Quaillet M; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, 91400, France.
  • Huang N; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, 91400, France.
  • Nicolas V; Université Paris-Saclay, MIPSIT Microscopy Facility, IPSIT, Orsay, 91400, France.
  • Boulogne C; Light Microscopy Facility Imagerie-Gif, CNRS - I2BC (present address), Gif-sur-Yvette, 91198, France.
  • Gillet C; Electron Microscopy Facility, Imagerie-Gif, Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, 91198, France.
  • Fattal E; Electron Microscopy Facility, Imagerie-Gif, Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, 91198, France.
  • Bochot A; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, 91400, France.
  • Hillaireau H; Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, Orsay, 91400, France.
Drug Deliv Transl Res ; 14(8): 2146-2157, 2024 Aug.
Article em En | MEDLINE | ID: mdl-38822092
ABSTRACT
While long-acting injectable treatments are gaining increasing interest in managing chronic diseases, the available drug delivery systems almost exclusively rely on hydrophobic matrixes, limiting their application to either hydrophobic drugs or large and hydrophilic molecules such as peptides. To address the technological lock for long-acting delivery systems tailored to small, hydrophilic drugs such as anticancer and antiviral nucleoside/nucleotide analogues, we have synthesized and characterized an original approach with a multi-scale structure (i) a nucleotide (adenosine triphosphate, ATP) is first incorporated in hydrophilic chitosan-Fe(III) nanogels; (ii) these nanogels are then transferred by freeze-drying and resuspension into a water-free, hydrophobic medium containing PLGA and an organic solvent, N-methyl-2-pyrrolidone. We show that this specific association allows an injectable and homogeneous dispersion, able to form in situ implants upon injection in physiological or aqueous environments. This system releases ATP in vitro without any burst effect in a two-step mechanism, first as nanogels acting as an intermediate reservoir over a week, then as free drug over several weeks. In vivo studies confirmed the potential of such nanostructured implants for sustained drug release following subcutaneous injection to mice hock, opening perspectives for sustained and targeted delivery through the lymphatic system.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Quitosana / Nanoestruturas / Interações Hidrofóbicas e Hidrofílicas Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Quitosana / Nanoestruturas / Interações Hidrofóbicas e Hidrofílicas Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article