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Givinostat-Liposomes: Anti-Tumor Effect on 2D and 3D Glioblastoma Models and Pharmacokinetics

  • Glioblastoma is the most common malignant brain tumor with a high grade of recurrence, invasiveness, and aggressiveness. Currently, there are no curative treatments; therefore, the discovery of novel molecules with anti-tumor activity or suitable drug delivery systems are important research topics. The aim of the present study was to investigate the anti-tumor activity of Givinostat, a pan-HDAC inhibitor, and to design an appropriate liposomal formulation to improve its pharmacokinetics profile and brain delivery. The present work demonstrates that the incorporation of Givinostat in liposomes composed of cholesterol and sphingomyelin improves its in vivo half-life and increases the amount of drug reaching the brain in a mouse model. Furthermore, this formulation preserves the anti-tumor activity of glioblastoma in 2D and 3D in vitro models. These features make liposome-Givinostat formulations potential candidates for glioblastoma therapy.

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Document Type:Article
Author:Lorenzo TaiarolORCiD, Chiara Bigogno, Silvia SesanaORCiD, Marcelo KraviczORCiD, Francesca Viale, Eleonora PozziORCiD, Laura Monza, Valentina Alda CarozziORCiD, Cristina MeregalliORCiD, Silvia ValtortaORCiD, Rosa Maria MorescoORCiD, Marcus Koch, Federica Barbugian, Laura RussoORCiD, Giulio DondioORCiD, Christian Steinkühler, Francesca ReORCiD
Parent Title (English):Cancers
First Page:2978
Year of first Publication:2022
Release Date:2022/09/11
Tag:HDCA inhibitor; brain; cancer; glioblastoma; liposomes
Impact:06.575 (2021)
Funding Information:IMMUN-HUB “Sviluppo di nuove molecole di seconda generazione per immunoterapia oncologica”, CUP E51B19000550007–Call HUB Ricerca e Innovazione, cofunded by POR FESR 2014–2020 (Regional Operational Programme, European Regional Development Fund).
Research Departments:Physikalische Analytik
DDC classes:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin, Gesundheit
Open Access:Open Access
Signature:INM 2022/082
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International