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Delivering Therapeutics to Glioblastoma: Overcoming Biological Constraints
Elza N Mathew1, Bethany C Berry1, Hong Wei Yang1
1Department of Neurological Surgery, University of Massachusetts Medical School, 55Lake Avenue North, Worcester, MA 01655, USA.
Abstract:
Glioblastoma multiforme is the most lethal intrinsic brain tumor. Even with the existing treatment regimen of surgery, radiation, and chemotherapy, the median survival time is only 15-23 months. The invasive nature of this tumor makes its complete removal very difficult, leading to a high recurrence rate of over 90%. Drug delivery to glioblastoma is challenging because of the molecular and cellular heterogeneity of the tumor, its infiltrative nature, and the blood-brain barrier. Understanding the critical characteristics that restrict drug delivery to the tumor is necessary to develop platforms for the enhanced delivery of effective treatments. In this review, we address the impact of tumor invasion, the molecular and cellular heterogeneity of the tumor, and the blood-brain barrier on the delivery and distribution of drugs using potential therapeutic delivery options such as convection-enhanced delivery, controlled release systems, nanomaterial systems, peptide-based systems, and focused ultrasound.
Insights
Glioblastoma treatment faces challenges due to tumor invasion and the blood-brain barrier. This review explores strategies to improve drug delivery for better glioblastoma multiforme outcomes.
Area of Science:
- Neuro-oncology
- Drug Delivery
- Biomedical Engineering
Background:
- Glioblastoma multiforme is an aggressive brain tumor with poor prognosis.
- Current treatments (surgery, radiation, chemotherapy) offer limited survival benefits.
- High recurrence rates stem from invasive tumor nature and incomplete resection.
Purpose of the Study:
- To review factors hindering drug delivery to glioblastoma.
- To explore advanced therapeutic delivery platforms for glioblastoma.
- To understand how tumor characteristics impact drug distribution.
Main Methods:
- Literature review of glioblastoma drug delivery challenges.
- Analysis of tumor invasion, heterogeneity, and blood-brain barrier effects.
- Evaluation of novel delivery systems: convection-enhanced delivery, controlled release, nanomaterials, peptide-based systems, and focused ultrasound.
Main Results:
- Tumor invasion and heterogeneity significantly impede drug penetration.
- The blood-brain barrier presents a major obstacle to systemic drug delivery.
- Various platforms show potential for overcoming these delivery challenges.
Conclusions:
- Enhanced drug delivery is crucial for improving glioblastoma treatment efficacy.
- Targeted delivery systems can overcome biological barriers.
- Further research into these platforms may lead to better patient outcomes.
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