Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma.

The blood-brain barrier (BBB) inhibits the entry of the majority of chemotherapeutic agents into the brain. Previous studies have illustrated the feasibility of drug delivery across the BBB using focused ultrasound (FUS) and microbubbles. Here, we investigated the effect of FUS-enhanced delivery of doxorubicin on survival in rats with and 9L gliosarcoma cells inoculated in the brain. Each rat received either: (1) no treatment (control; N = 11), (2) FUS only (N = 9), (3) IV liposomal doxorubicin (DOX only; N = 17), or (4) FUS with concurrent IV injections of liposomal doxorubicin (FUS+DOX; N = 20). Post-treatment by magnetic resonance imaging (MRI) showed that FUS+DOX reduced tumor growth compared with DOX only. Further, we observed a modest but significant increase in median survival time after a single treatment FUS+DOX treatment (p = 0.0007), whereas neither DOX nor FUS had any significant impact on survival on its own. These results suggest that combined ultrasound-mediated BBB disruption may significantly increase the antineoplastic efficacy of liposomal doxorubicin in the brain.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To determine whether focused ultrasound-enhanced delivery of liposomal doxorubicin across the blood–brain barrier improves tumor control and survival in rats bearing intracranial 9L gliosarcoma.

Animal model / Human subject Rat (Rattus spp.), strain: not reported, age: not reported, sex: not reported

Disease model glioma (9L gliosarcoma brain tumor model)

Cargo name and characteristics Liposomal doxorubicin (chemotherapeutic small-molecule doxorubicin encapsulated in liposomal nanoparticle formulation; administered intravenously)

Route of administration intravenous

Outcomes and Safety

Summary of Outcomes FUS-mediated BBB disruption combined with intravenous liposomal doxorubicin reduced tumor growth on MRI and produced a modest but significant increase in median survival in rats bearing 9L gliosarcoma, whereas FUS or doxorubicin alone had no significant effect. The study did not report testing multiple focused ultrasound parameter variants; only the combined FUS+DOX treatment was reported as effective.

Safety-related matter The paper did not report any safety concerns or adverse effects associated with focused ultrasound, liposomal doxorubicin, or their combination; no adverse effects were mentioned.

Brain Region

Visualization unavailable

Ultrasound Parameters

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

Treatment frequency Single

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