Pitt Shield

Focused Delivery of Chemotherapy to Augment Surgical Management of Brain Tumors.

Authors: Mehkri Y, Woodford S, Pierre K, Dagra A, Hernandez J, Reza Hosseini Siyanaki M, Azab M, Lucke-Wold B

Chemotherapy as an adjuvant therapy that has largely failed to significantly improve outcomes for aggressive brain tumors; some reasons include a weak blood brain barrier penetration and tumor heterogeneity. Recently, there has been interest in designing effective ways to deliver chemotherapy to the tumor. In this review, we discuss the mechanisms of focused chemotherapies that are currently under investigation. Nanoparticle delivery demonstrates both a superior permeability and retention. However, thus far, it has not demonstrated a therapeutic efficacy for brain tumors. Convection-enhanced delivery is an invasive, yet versatile method, which appears to have the greatest potential. Other vehicles, such as angiopep-2 decorated gold nanoparticles, polyamidoamine dendrimers, and lipid nanostructures have demonstrated efficacy through sustained release of focused chemotherapy and have either improved cell death or survival in humans or animal models. Finally, focused ultrasound is a safe and effective way to disrupt the blood brain barrier and augment other delivery methods. Clinical trials are currently underway to study the safety and efficacy of these methods in combination with standard of care.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To review and discuss current mechanisms and delivery methods for focused chemotherapy aimed at improving drug delivery to aggressive brain tumors.
Disease model Aggressive brain tumors
Cargo name and characteristics Chemotherapy (small-molecule chemotherapeutic agents); nanoparticles: angiopep-2–decorated gold nanoparticles (targeted gold nanoparticle with angiopep-2 peptide), polyamidoamine (PAMAM) dendrimers (dendrimer nanoparticle carrier), lipid nanostructures/lipid nanoparticles (lipid-based nanocarriers)
Route of administration Convection-enhanced delivery (intracerebral/intratumoral infusion); nanoparticle-based delivery (e.g., angiopep-2-decorated gold nanoparticles, polyamidoamine dendrimers, lipid nanostructures); focused ultrasound-mediated blood–brain barrier disruption to augment delivery

Outcomes and Safety

Summary of Outcomes Focused ultrasound safely and effectively disrupts the blood-brain barrier to augment chemotherapy delivery, and other delivery strategies (nanoparticles, convection-enhanced delivery, angiopep-2–decorated gold nanoparticles, polyamidoamine dendrimers, lipid nanostructures) showed improved drug retention, increased tumor cell death, or survival in models. The review did not report specific focused ultrasound parameters or compare multiple FUS parameter sets.
Safety-related matter The review states focused ultrasound is a safe and effective way to disrupt the blood–brain barrier and notes that clinical trials are underway to study the safety and efficacy of these delivery methods; no adverse effects are reported in the text.

Brain Region

Visualization unavailable

Ultrasound Parameters

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

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