Vortioxetine: A potential drug for repurposing for glioblastoma treatment via a microsphere local delivery system

Wang, Yu, Siebzehnrubl, Dorit, Weller, Michael, Weiss, Tobias, Siebzehnrubl, Florian A. ORCID: https://orcid.org/0000-0001-8411-8775 and Newland, Ben ORCID: https://orcid.org/0000-0002-5214-2604 2025. Vortioxetine: A potential drug for repurposing for glioblastoma treatment via a microsphere local delivery system. ACS Biomaterials Science & Engineering 10.1021/acsbiomaterials.5c00068

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Abstract

Drug repurposing is an attractive route for finding new therapeutics for brain cancers such as glioblastoma. Local administration of drugs to brain tumors or the postsurgical resection cavity holds promise to deliver a high dose to the target site with minimal off-target effects. Drug delivery systems aim to sustain the release of the drug at the target site but typically exhibit drawbacks such as a poor safety profile, uncontrolled/rapid drug release, or poor control over synthesis parameters/material dimensions. Herein, we analyzed the antidepressant vortioxetine and showed in vitro that it causes a greater loss of viability in glioblastoma cells than it does to normal primary human astrocytes. We developed a new droplet microfluidic-based emulsion method to reproducibly produce vortioxetine-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres with tight size control (36.80 ± 1.96 μm). The drug loading efficiency was around 90% when 9.1% (w/w) drug was loaded into the microspheres, and drug release could be sustained for three to 4 weeks. The vortioxetine microspheres showed robust antiglioblastoma efficacy in both 2D monolayer and 3D spheroid patient-derived glioblastoma cells, highlighting the potential of combining an antidepressant with sustained local delivery as a new therapeutic strategy.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Biosciences Schools > Pharmacy
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2025-04-01
Publisher:	American Chemical Society
ISSN:	2373-9878
Date of First Compliant Deposit:	11 April 2025
Last Modified:	11 Apr 2025 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/177607

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