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Published on: June 16, 2022
In Vitro Glioblastoma Model on a Plate for Localized Drug Release Study from a 3D-Printed Drug-Eluted Hydrogel Mesh
Behnad Chehri1, Kaiwen Liu1, Golnaz Vaseghi1
1Laboratory for Innovations in Microengineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, BC V8P 5C2, Canada.
Abstract:
Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that has limited treatment options. Current standard therapies, including surgery followed by radiotherapy and chemotherapy, are not very effective due to the rapid progression and recurrence of the tumor. Therefore, there is an urgent need for more effective treatments, such as combination therapy and localized drug delivery systems that can reduce systemic side effects. Recently, a handheld printer was developed that can deliver drugs directly to the tumor site. In this study, the feasibility of using this technology for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) to treat glioblastoma is showcased. A flexible drug-loaded mesh (GlioMesh) loaded with poly (lactic-co-glycolic acid) (PLGA) microparticles is printed, which shows the sustained release of both drugs for up to a month. The effectiveness of the printed drug-eluting mesh in terms of tumor toxicity and invasion inhibition is evaluated using a 3D micro-physiological system on a plate and the formation of GBM tumoroids within the microenvironment. The proposed in vitro model can identify the effective combination doses of TMZ and DFP in a sustained drug delivery platform. Additionally, our approach shows promise in GB therapy by enabling localized delivery of multiple drugs, preventing off-target cytotoxic effects.
Insights
A novel handheld printer enables localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) using a drug-eluting mesh for glioblastoma treatment. This approach demonstrates sustained drug release and effective tumor inhibition in vitro.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery Systems
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited effective treatment options.
- Current therapies often fail due to rapid tumor progression and recurrence, necessitating novel treatment strategies.
- Localized drug delivery systems are crucial for reducing systemic side effects and improving therapeutic efficacy.
Purpose of the Study:
- To evaluate the feasibility of a handheld printer for localized co-delivery of temozolomide (TMZ) and deferiprone (DFP) for glioblastoma treatment.
- To assess the sustained drug release profile of a flexible drug-loaded mesh (GlioMesh).
- To investigate the in vitro efficacy of the GlioMesh in inhibiting GBM tumor toxicity and invasion.
Main Methods:
- Development of a flexible drug-loaded mesh (GlioMesh) using poly(lactic-co-glycolic acid) (PLGA) microparticles for sustained release of TMZ and DFP.
- Utilizing a handheld printer for localized drug deposition directly onto the tumor site.
- Evaluation of GlioMesh efficacy using a 3D micro-physiological system and GBM tumoroids to assess tumor toxicity and invasion inhibition.
Main Results:
- The printed GlioMesh demonstrated sustained release of both TMZ and DFP for up to one month.
- The in vitro model successfully identified effective combination doses for TMZ and DFP.
- The localized delivery approach showed promise in inhibiting GBM tumor toxicity and invasion, preventing off-target effects.
Conclusions:
- A handheld printing technology enables localized co-delivery of TMZ and DFP via a sustained-release GlioMesh for glioblastoma therapy.
- The developed 3D in vitro model is effective in identifying optimal drug combinations and evaluating therapeutic potential.
- This localized drug delivery strategy offers a promising approach to enhance glioblastoma treatment by minimizing systemic toxicity.
