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Vascular and cellular damage photoinduced in chorioallantoic membrane model by Foslip® and Fospeg® : influence of mTHPC release from liposomes

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Garrier, Julie | Reshetov, Vadim | François, Aurélie | Gräfe, Susanna | Guillemin, François | Zorin, Vladimir | Bezdetnaya, Lina

Edité par CCSD -

International audience. Context: Tumoricidal photodynamic therapy (PDT) efficacy implicates the combination of direct cellular and indirect vascular damage supported by an immune activation. It was demonstrated that the success of mTHPC-PDT depends particularly on tumoral vascular damage (Garrier et al., 2010). Recently developed liposomal formulations of mTHPC (Foslip®, Fospeg®) aim to improve the pharmacokinetic properties of the photosensitizer. However, mTHPC release from liposomal formulations en route to target tissue may have a direct impact on drug delivery and efficacy. Materials & Methods: Foslip® and Fospeg® were intravenously administered into tumor-free and tumor-xenografted chick ChorioAllantoic Membrane (CAM). mTHPC release was estimated by photoinduced fluorescence quenching. PDT treatment was realized with different drug light intervals (DLIs) corresponding to partial or complete mTHPC release. Photothrombic activity was evaluated by macroscopy. CAM and tumor damage were studied by histology and pharmacokinetic profiles were established by HPLC. Results: The release of mTHPC from Foslip® and the destruction of carriers were significantly faster than from Fospeg®. The photothrombic activity in tumor-free CAM was more important for Foslip® and resulted in up to complete occlusion of the treated area for the longer DLI. Histological analysis confirmed higher tissue damage by Foslip® with characteristic morphological changes. In contrast, Fospeg® demonstrated a better accumulation in tumor xenografted on CAM resulting in a significant photoinduced necrosis rate compared to Foslip®. Conclusion: Conventional formulation (Foslip®) presented a better efficacy to trigger vascular damage linked to a rapid mTHPC release from liposomes contrary to the stabilized formulation (Fospeg®), where more time is required for uptake by endothelial cells. On the opposite, longer circulation and slower drug release of Fospeg® allowed an increased tumoral accumulation related to the Enhanced Permeability and Retention effect. As a consequence, Fospeg® showed better efficacy to trigger neoplastic cells photodamage.

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