title: Photodynamic therapy with conventional and PEGylated liposomal formulations of mTHPC (temoporfin): comparison of treatment efficacy and distribution characteristics in vivo.
abstract: A major challenge in the application of a nanoparticle-based drug delivery system for anticancer agents is the knowledge of the critical properties that influence their in vivo behavior and the therapeutic performance of the drug. The effect of a liposomal formulation, as an example of a widely-used delivery system, on all aspects of the drug delivery process, including the drug's behavior in blood and in the tumor, has to be considered when optimizing treatment with liposomal drugs, but that is rarely done. This article presents a comparison of conventional (Foslip®) and polyethylene glycosylated (Fospeg®) liposomal formulations of temoporfin (meta-tetra[hydroxyphenyl]chlorin) in tumor-grafted mice, with a set of comparison parameters not reported before in one model. Foslip® and Fospeg® pharmacokinetics, drug release, liposome stability, tumor uptake, and intratumoral distribution are evaluated, and their influence on the efficacy of the photodynamic treatment at different light-drug intervals is discussed. The use of whole-tumor multiphoton fluorescence macroscopy imaging is reported for visualization of the in vivo intratumoral distribution of the photosensitizer. The combination of enhanced permeability and retention-based tumor accumulation, stability in the circulation, and release properties leads to a higher efficacy of the treatment with Fospeg® compared to Foslip®. A significant advantage of Fospeg® lies in a major decrease in the light-drug interval, while preserving treatment efficacy.
authors.affiliation: Université de lorraine, centre de Recherche en Automatique de Nancy, Campus Sciences, Vandœuvre-lès-Nancy, France ; Centre National de la Recherche Scientifique, Centre de Recherche en Automatique de Nancy, France ; Laboratory of Biophysics and Biotechnology, Physics Faculty, Belarusian State University, Minsk, Belarus.
authors.forename: Vadzim
authors.initials: V
authors.lastname: Reshetov
authors.forename: Henri-Pierre
authors.initials: HP
authors.lastname: Lassalle
authors.forename: Aurélie
authors.initials: A
authors.lastname: François
authors.forename: Dominique
authors.initials: D
authors.lastname: Dumas
authors.forename: Sebastien
authors.initials: S
authors.lastname: Hupont
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.forename: Vasco
authors.initials: V
authors.lastname: Filipe
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.forename: François
authors.initials: F
authors.lastname: Guillemin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zorin
authors.forename: Lina
authors.initials: L
authors.lastname: Bezdetnaya
mesh_terms: D000818:Animals; D019073:HT29 Cells; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry*; D008652:Mesoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D008652:Mesoporphyrins; D053769:Nanocapsules; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin
keywords: biodistribution; drug release; liposomal pharmacokinetics; liposomes; mTHPC; photodynamic therapy