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Interaction of Liposomal Formulations of Meta-tetra(hydroxyphenyl)chlorin (Temoporfin) with Serum Proteins: Protein Binding and Liposome Destruction

Authors

  • Vadzim Reshetov,

    1. Centre de Recherche en Automatique de Nancy, Université de Lorraine, CNRS UMR 7039, Centre Alexis Vautrin, Vandœuvre-Les-Nancy, France
    2. Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, Minsk, Belarus
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  • Vladimir Zorin,

    1. Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, Minsk, Belarus
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  • Agnieszka Siupa,

    1. Nanosight Ltd., Amesbury, UK
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  • Marie-Ange D’Hallewin,

    1. Centre de Recherche en Automatique de Nancy, Université de Lorraine, CNRS UMR 7039, Centre Alexis Vautrin, Vandœuvre-Les-Nancy, France
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  • François Guillemin,

    1. Centre de Recherche en Automatique de Nancy, Université de Lorraine, CNRS UMR 7039, Centre Alexis Vautrin, Vandœuvre-Les-Nancy, France
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  • Lina Bezdetnaya

    Corresponding author
    1. Centre de Recherche en Automatique de Nancy, Université de Lorraine, CNRS UMR 7039, Centre Alexis Vautrin, Vandœuvre-Les-Nancy, France
      Corresponding author email: l.bolotine@nancy.unicancer.fr (Lina Bezdetnaya)
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Corresponding author email: l.bolotine@nancy.unicancer.fr (Lina Bezdetnaya)

Abstract

mTHPC is a non polar photosensitizer used in photodynamic therapy. To improve its solubility and pharmacokinetic properties, liposomes were proposed as drug carriers. Binding of liposomal mTHPC to serum proteins and stability of drug carriers in serum are of major importance for PDT efficacy; however, neither was reported before. We studied drug binding to human serum proteins using size-exclusion chromatography. Liposomes destruction in human serum was measured by nanoparticle tracking analysis (NTA). Inclusion of mTHPC into conventional (Foslip®) and PEGylated (Fospeg®) liposomes does not affect equilibrium serum protein binding compared with solvent-based mTHPC. At short incubation times the redistribution of mTHPC from Foslip® and Fospeg® proceeds by both drug release and liposomes destruction. At longer incubation times, the drug redistributes only by release. The release of mTHPC from PEGylated vesicles is delayed compared with conventional liposomes, alongside with greatly decreased liposomes destruction. Thus, for long-circulation times the pharmacokinetic behavior of Fospeg® could be influenced by a combination of protein- and liposome-bound drug. The study highlights the modes of interaction of photosensitizer-loaded nanovesicles in serum to predict optimal drug delivery and behavior in vivo in preclinical models, as well as the novel application of NTA to assess the destruction of liposomes.

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