Interaction of liposomal formulations of meta-tetra(hydroxyphenyl)chlorin (Temoporfin) with serum proteins: protein binding and liposome destruction.

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 to 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 to 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 pre-clinical models, as well as the novel application of NTA to assess the destruction of liposomes.
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Photochemistry and Photobiology, Wiley, 2012, 88 (5), pp.1256-1264. 〈10.1111/j.1751-1097.2012.01176.x〉
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https://hal.archives-ouvertes.fr/hal-00701915
Contributeur : Marie Ange D'Hallewin <>
Soumis le : lundi 28 mai 2012 - 09:57:34
Dernière modification le : mardi 22 septembre 2015 - 01:11:49

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Vadim Reshetov, Vladimir Zorin, Agnieszka Siupa, Marie Ange D'Hallewin, François Guillemin, et al.. Interaction of liposomal formulations of meta-tetra(hydroxyphenyl)chlorin (Temoporfin) with serum proteins: protein binding and liposome destruction.. Photochemistry and Photobiology, Wiley, 2012, 88 (5), pp.1256-1264. 〈10.1111/j.1751-1097.2012.01176.x〉. 〈hal-00701915〉

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