Overview of Current Drug Delivery Methods Across the Blood–Brain Barrier for the Treatment of Primary Brain Tumors

Abstract

Existing drug delivery methods have not led to a significant increase in survival for patients with malignant primary brain tumors. While the combination of conventional therapies consisting of surgery, radiotherapy, and chemotherapy has improved survival for some types of brain tumors (e.g., WNT medulloblastoma), other types of brain tumors (e.g., glioblastoma and diffuse midline glioma) still have a poor prognosis. The reason for the differences in response can be largely attributed to the blood-brain barrier (BBB), a specialized structure at the microvasculature level that regulates the transport of molecules across the blood vessels into the brain parenchyma. This structure hampers the delivery of most chemotherapeutic agents for the treatment of primary brain tumors. Several drug delivery methods such as nanoparticles, convection enhanced delivery, focused ultrasound, intranasal delivery, and intra-arterial delivery have been developed to overcome the BBB in primary brain tumors. However, prognosis of most primary brain tumors still remains poor. The heterogeneity of the BBB in primary brain tumors and the distinct vasculature of tumors make it difficult to design a drug delivery method that targets the entire tumor. Drug delivery methods that combine strategies such as focused ultrasound and nanoparticles might be a more successful approach. However, more research is needed to optimize and develop new drug delivery techniques to improve survival of patients with primary brain tumors.

Radiosensitization in Pediatric High-Grade Glioma: Targets, Resistance and Developments

“…Despite the promising radio-enhancing effects of the agents addressed in this review, a recurrent problem with small molecule inhibitors remains the limited distribution through the brain due to their inability to cross the BBB. Although the BBB is often disrupted in aHGG, the integrity of this barrier in pHGG is often more intact, especially in DMG, but also appears to have a heterogeneous representation ( 90 ). Regardless of BBB integrity within the tumor, the ability to penetrate the brain remains a prerequisite for any compound used in these diffusely growing brain tumors as tumor cells can migrate into regions of the brain with an intact BBB.…”

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

“…Pericytes are derived from the neural crest and are integrated into the endothelial and astrocyte functions at the neurovascular unit, and they regulate the BBB [ 153 ]. Pericytes appear to form a continuum from arteriole to venule and share a basement membrane with endothelial cells.…”

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery

“…BBs not only impede treatment options but diminish bioavailability of drugs in regions protected by BBs, which can lead to increased drug resistance in bacteria and other pathogens. Moreover, engineered nanoparticles and drug therapies for crossing BBs could potentially dysregulate or suppress biochemical pathways and increase risks of side effects [ 3 , 4 , 5 , 6 ].…”