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.
Highlights
Glioblastoma multiforme (GBM) is characterized by rapid cell proliferation and extensive invasion of tumor cells into the surrounding brain, making complete removal of the tumor impossible [11]
We focus on the use of convection-enhanced delivery, controlled release systems, nanomaterial will focus on the use of convection-enhanced delivery, controlled release systems, systems, peptide-based therapeutics and focused ultrasound (FUS) for the treatment of this nanomaterial systems, peptide-based therapeutics and focused ultrasound (FUS) for the aggressive tumor
The blood–brain barrier is composed of a highly specialized circuit of blood vessels that are lined by brain microvascular endothelial cells (BMEC), the cell–cell junctions between which restrict the entry of potentially harmful substances into the brain
Summary
GBM is characterized by rapid cell proliferation and extensive invasion of tumor cells into the surrounding brain, making complete removal of the tumor impossible [11] These features lead to a high recurrence rate, even with the current treatment regimen of maximum safe surgical removal, radiation therapy and temozolomide chemotherapy. Numerous drug therapies directed against GBM have shown promising results in in vitro assays, but all have had limited success in vivo This is due in part to the diffuse, heterogeneous nature of the tumor, and the blood–brain barrier that limits the ability of many drugs to enter the brain parenchyma. We discuss the impact that molecular and cellular tumor heterogeneity, tumor dispersion and the blood–brain barrier have on the delivery and of pharmacological agents to GBM.
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