Delivering Therapeutics to Glioblastoma: Overcoming Biological Constraints.

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.

Introduction

Purpose Drug delivery WITHOUT BBB opening

Study Objective To review how tumor invasion, molecular and cellular heterogeneity, and the blood–brain barrier limit drug delivery to glioblastoma and to evaluate potential therapeutic delivery strategies to overcome these barriers.

Disease model Glioblastoma multiforme (glioblastoma)

Route of administration Convection-enhanced delivery (direct intracerebral/intratumoral infusion); controlled-release systems (local/implantable intracranial delivery); nanomaterial and peptide-based systems (typically systemic, e.g., intravenous); focused ultrasound-mediated BBB opening (used in conjunction with intravenous delivery)

Outcomes and Safety

Summary of Outcomes Tumor invasion, molecular and cellular heterogeneity, and the blood–brain barrier are major biological barriers that critically restrict drug delivery and distribution in glioblastoma; the review discusses strategies to enhance delivery including convection-enhanced delivery, controlled release, nanomaterials, peptide-based systems, and focused ultrasound. The paper did not test focused ultrasound parameters and therefore reports no specific ultrasound parameter settings as successful.

Duration of biological effect 15–23 months

Safety-related matter No safety concerns or adverse effects were mentioned in the provided text.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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