Morgane Renault-Mahieux1,2, Victoire Vieillard2, Johanne Seguin1, Philippe Espeau1, Dang Tri Le1, René Lai-Kuen3, Nathalie Mignet1, Muriel Paul2, Karine Andrieux1. 1. Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris, 4 Avenue de l'Observatoire, 75006 Paris, France. 2. Henri Mondor Hospital Group, Pharmacy Department, Assistance Publique-Hôpitaux de Paris (AP-HP), 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. 3. UMS3612 Centre National de la Recherche Scientifique (CNRS), US25 Institut NATIONAL de la Santé et de la Recherche Médicale (INSERM), Plateforme Mutualisée de l'Institut du Médicament (P-MIM), Plateau Technique Imagerie Cellulaire et Moléculaire, Université de Paris, 75006 Paris, France.
Abstract
(1) Background: Glioblastoma (GBM) is the most frequent cerebral tumor. It almost always relapses and there is no validated treatment for second-line GBM. We proposed the coencapsulation of fisetin and cisplatin into liposomes, aiming to (i) obtain a synergistic effect by combining the anti-angiogenic effect of fisetin with the cytotoxic effect of cisplatin, and (ii) administrate fisetin, highly insoluble in water. The design of a liposomal formulation able to encapsulate, retain and deliver both drugs appeared a challenge. (2) Methods: Liposomes with increasing ratios of cholesterol/DOPC were prepared and characterized in term of size, PDI and stability. The incorporation of fisetin was explored using DSC. The antiangiogneic and cytotoxic activities of the selected formulation were assayed in vitro. (3) Results: We successfully developed an optimized liposomal formulation incorporating both drugs, composed by DOPC/cholesterol/DODA-GLY-PEG2000 at a molar ratio of 75.3/20.8/3.9, with a diameter of 173 ± 8 nm (PDI = 0.12 ± 0.01) and a fisetin and cisplatin drug loading of 1.7 ± 0.3% and 0.8 ± 0.1%, respectively, with a relative stability over time. The maximum incorporation of fisetin into the bilayer was determined at 3.2% w/w. Then, the antiangiogenic activity of fisetin was maintained after encapsulation. The formulation showed an additive effect of cisplatin and fisetin on GBM cells; (4) Conclusions: The developed co-loaded formulation was able to retain the activity of fisetin, was effective against GBM cells and is promising for further in vivo experimentations.
(1) Background: Glioblastoma (GBM) is the most frequent cerebral tumor. It almost always relapses and there is no validated treatment for second-line GBM. We proposed the coencapsulation of fisetin and cisplatin into liposomes, aiming to (i) obtain a synergistic effect by combining the anti-angiogenic effect of fisetin with the cytotoxic effect of cisplatin, and (ii) administrate fisetin, highly insoluble in water. The design of a liposomal formulation able to encapsulate, retain and deliver both drugs appeared a challenge. (2) Methods: Liposomes with increasing ratios of cholesterol/DOPC were prepared and characterized in term of size, PDI and stability. The incorporation of fisetin was explored using DSC. The antiangiogneic and cytotoxic activities of the selected formulation were assayed in vitro. (3) Results: We successfully developed an optimized liposomal formulation incorporating both drugs, composed by DOPC/cholesterol/DODA-GLY-PEG2000 at a molar ratio of 75.3/20.8/3.9, with a diameter of 173 ± 8 nm (PDI = 0.12 ± 0.01) and a fisetin and cisplatin drug loading of 1.7 ± 0.3% and 0.8 ± 0.1%, respectively, with a relative stability over time. The maximum incorporation of fisetin into the bilayer was determined at 3.2% w/w. Then, the antiangiogenic activity of fisetin was maintained after encapsulation. The formulation showed an additive effect of cisplatin and fisetin on GBM cells; (4) Conclusions: The developed co-loaded formulation was able to retain the activity of fisetin, was effective against GBM cells and is promising for further in vivo experimentations.
Authors: Nathalie Mignet; Johanne Seguin; Miriam Ramos Romano; Laura Brullé; Yasmine S Touil; Daniel Scherman; Michel Bessodes; Guy G Chabot Journal: Int J Pharm Date: 2011-05-06 Impact factor: 5.875
Authors: Johanne Seguin; Laura Brullé; Renaud Boyer; Yen Mei Lu; Miriam Ramos Romano; Yasmine S Touil; Daniel Scherman; Michel Bessodes; Nathalie Mignet; Guy G Chabot Journal: Int J Pharm Date: 2013-02-01 Impact factor: 5.875
Authors: Sergey A Shein; Ilya I Kuznetsov; Tatiana O Abakumova; Pavel S Chelushkin; Pavel A Melnikov; Anna A Korchagina; Dmitry A Bychkov; Irina F Seregina; Mikhail A Bolshov; Alexander V Kabanov; Vladimir P Chekhonin; Natalia V Nukolova Journal: Mol Pharm Date: 2016-10-03 Impact factor: 4.939
Authors: Henry S Friedman; Michael D Prados; Patrick Y Wen; Tom Mikkelsen; David Schiff; Lauren E Abrey; W K Alfred Yung; Nina Paleologos; Martin K Nicholas; Randy Jensen; James Vredenburgh; Jane Huang; Maoxia Zheng; Timothy Cloughesy Journal: J Clin Oncol Date: 2009-08-31 Impact factor: 44.544
Authors: Natalia Zisman; Nancy Dos Santos; Sharon Johnstone; Alan Tsang; David Bermudes; Lawrence Mayer; Paul Tardi Journal: Chemother Res Pract Date: 2011-01-24
Authors: Malaka Ameratunga; Nick Pavlakis; Helen Wheeler; Robin Grant; John Simes; Mustafa Khasraw Journal: Cochrane Database Syst Rev Date: 2018-11-22