Vortioxetine: A Potential Drug for Repurposing for Glioblastoma Treatment via a Microsphere Local Delivery System.

in ACS biomaterials science & engineering by Yu Wang, Dorit Siebzehnrubl, Michael Weller, Tobias Weiss, Florian A Siebzehnrubl, Ben Newland

TLDR

  • Researchers repurpose antidepressant vortioxetine for glioblastoma treatment and develop a novel microsphere delivery method for sustained local release.
  • Vortioxetine microspheres exhibit robust antiglioblastoma efficacy in patient-derived cells, with sustained drug release and high loading efficiency.
  • This study suggests a new therapeutic strategy combining an antidepressant with local delivery for glioblastoma treatment.

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 showedthat 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--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.

Overview

  • The study aims to repurpose an antidepressant, vortioxetine, for treating glioblastoma, a type of brain cancer.
  • The study developed a droplet microfluidic-based emulsion method to produce vortioxetine-loaded poly(lactic--glycolic) acid (PLGA) microspheres with tight size control and high drug loading efficiency.
  • The primary objective of the study is to investigate the potential of combining an antidepressant with sustained local delivery as a new therapeutic strategy for glioblastoma treatment.

Comparative Analysis & Findings

  • The study found that vortioxetine causes a greater loss of viability in glioblastoma cells than it does to normal primary human astrocytes.
  • The vortioxetine microspheres showed robust antiglioblastoma efficacy in both 2D monolayer and 3D spheroid patient-derived glioblastoma cells.
  • The drug release from the microspheres could be sustained for three to 4 weeks, with a high drug loading efficiency of around 90%.

Implications and Future Directions

  • The study's findings suggest that vortioxetine may be a promising therapeutic agent for glioblastoma treatment, particularly when combined with sustained local delivery using microspheres.
  • Future studies could investigate the use of this approach in animal models or clinical trials to assess its efficacy and safety.
  • Additional research could focus on optimizing the microsphere design and delivery method to improve drug release and targeting of glioblastoma cells.
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