In Vitro Blood-Brain Barrier Permeability and Cytotoxicity of an Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models

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Luebtow , M M , Oerter , S , Quader , S , Jeanclos , E , Cubukova , A , Krafft , M , Haider , M S , Schulte , C , Meier , L , Rist , M , Sampetrean , O , Kinoh , H , Gohla , A , Kataoka , K , Appelt-Menzel , A & Luxenhofer , R 2020 , ' In Vitro Blood-Brain Barrier Permeability and Cytotoxicity of an Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models ' , Molecular Pharmaceutics , vol. 17 , no. 6 , pp. 1835-1847 . https://doi.org/10.1021/acs.molpharmaceut.9b01117

Title: In Vitro Blood-Brain Barrier Permeability and Cytotoxicity of an Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models
Author: Luebtow, Michael M.; Oerter, Sabrina; Quader, Sabina; Jeanclos, Elisabeth; Cubukova, Alevtina; Krafft, Marion; Haider, Malik Salman; Schulte, Clemens; Meier, Laura; Rist, Maximilian; Sampetrean, Oltea; Kinoh, Hiroaki; Gohla, Antje; Kataoka, Kazunori; Appelt-Menzel, Antje; Luxenhofer, Robert
Contributor organization: Polymers
Department of Chemistry
Date: 2020-06-01
Language: eng
Number of pages: 13
Belongs to series: Molecular Pharmaceutics
ISSN: 1543-8384
DOI: https://doi.org/10.1021/acs.molpharmaceut.9b01117
URI: http://hdl.handle.net/10138/329218
Abstract: Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the family of statins have been suggested as therapeutic options in various tumors. Atorvastatin is a statin with the potential to cross the blood-brain barrier; however, the concentrations necessary for a cytotoxic effect against cancer cells exceed the concentrations achievable via oral administration, which made the development of a novel atorvastatin formulation necessary. We characterized the drug loading and basic physicochemical characteristics of micellar atorvastatin formulations and tested their cytotoxicity against a panel of different glioblastoma cell lines. In addition, activity against tumor spheroids formed from mouse glioma and mouse cancer stem cells, respectively, was evaluated. Our results show good activity of atorvastatin against all tested cell lines. Interestingly, in the three-dimensional (3D) models, growth inhibition was more pronounced for the micellar formulation compared to free atorvastatin. Finally, atorvastatin penetration across a blood-brain barrier model obtained from human induced-pluripotent stem cells was evaluated. Our results suggest that the presented micelles may enable much higher serum concentrations than possible by oral administration; however, if transport across the blood-brain barrier is sufficient to reach the therapeutic atorvastatin concentration for the treatment of glioblastoma via intravenous administration remains unclear.
Subject: drug-loaded micelles
poly(2-oxazoline)
poly(2-oxazine)
nanomedicine
human induced-pluripotent stem cells
cancer stem cells
CANCER STEM-CELLS
BLOCK-COPOLYMERS
SPHEROID CULTURE
DRUG-DELIVERY
STATINS
RESISTANCE
INHIBITION
TRANSPORT
GLIOMA
VIVO
317 Pharmacy
116 Chemical sciences
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


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