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Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo.

ABSTRACT: Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg.kg-1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg.kg-1) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.

SUBMITTER: Michy T

PROVIDER: S-EPMC6896159 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo.

Michy Thierry T Massias Thibault T Bernard Claire C Vanwonterghem Laetitia L Henry Maxime M Guidetti Mélanie M Royal Guy G Coll Jean-Luc JL Texier Isabelle I Josserand Véronique V Hurbin And Amandine AA

Cancers 20191108 11

Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and ...[more]

PMID: 31717427

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Project description:Background and methodsA new cyclosporin A-loaded, PEGylated chitosan-modified lipid-based nanoparticle was developed to improve upon the formulation of cyclosporin A. PEGylated chitosan, synthesized in three steps using mild reaction conditions, was used to modify the nanoparticles. Cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were prepared using an emulsification/solvent evaporation method. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were measured by high-performance liquid chromatography. The average size of the nanoparticles was determined by transmission electron microscopy and dynamic light scattering. The pharmacokinetic behavior of the nanoparticles was investigated in rabbits after intravenous injection. Cyclosporin A concentrations in a whole blood sample were analyzed by high-performance liquid chromatography using tamoxifen as the internal standard. The pharmacokinetic parameters were calculated using the 3p87 software program.ResultsFourier transform infrared spectroscopy and nuclear magnetic resonance confirmed the structure of PEGylated chitosan. The drug content and encapsulation efficiency of the cyclosporin A-loaded, PEGylated chitosan-modified nanoparticles were 37.04% and 69.22%, respectively. The average size of the nanoparticles was 89.4 nm. The nanoparticles released 30% cyclosporin A-loaded in 48 hours in vitro, with no initial burst release. The mode of release in vitro was prone to bulk erosion. The in vivo results showed the biological half-life of the elimination phase (t(1/2β)) of the nanoparticles was 21 times longer than that of the cyclosporin A solution, and the area under the curve for the nanoparticles was 25.8 times greater than that of the cyclosporin A solution.ConclusionModification of PEGylated chitosan prolonged the retention time of the nanoparticles in the circulatory system and improved the bioavailability of cyclosporin A.

Dataset Information

Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo.

Publications

Verteporfin-Loaded Lipid Nanoparticles Improve Ovarian Cancer Photodynamic Therapy In Vitro and In Vivo.

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