Ultrasound-mediated delivery of brain-penetrating nanoparticles across the blood-tumor barrier

Kelsie Timbie,Richard Price,Elizabeth Nance,Justin Hanes,Clark Zhang,Ji Song,Wilson Miller

doi:10.1186/2050-5736-3-s1-p34

Kelsie Timbie, Richard Price + Show 5 more

Open Access

https://doi.org/10.1186/2050-5736-3-s1-p34

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Abstract

The intact blood-brain barrier (BBB) presents a major obstacle for drug delivery to the brain. In addition, both high interstitial pressure and a nanoporous electrostatically charged tissue composition, produce a “blood-tumor barrier” (BTB), further complicating the treatment of diseases like glioblastoma. Focused ultrasound (FUS) in conjunction with microbubbles (MB) has been shown to cause reversible, localized disruption of the BBB. Incorporating MR guidance with FUS offers the ability to exquisitely target the BBB disruption to specific regions of the brain, thereby permitting drug delivery in a highly localized manner. This work examines the ability of MR guided FUS to deliver highly specialized brain-penetrating nanoparticles (NP) across both the BBB and the BTB in tumor-bearing rats. NPs were 60 nm in diameter and covered with an exceptionally dense brush layer of PEG to permit excellent diffusion through brain tissue. Initial studies utilized fluorescent polystyrene tracer particles to measure NP delivery and inform dosing of cisplatin-loaded biodegradable NPs.

Highlights

Background/introduction The intact blood-brain barrier (BBB) presents a major obstacle for drug delivery to the brain
Mounted sections were stained with BS-I lectin to reveal endothelial cells (ECs) and imaged with fluorescent microscopy
Initial studies with fluorescent tracer particles indicate that Focused ultrasound (FUS) and MBs are capable of disrupting the blood-tumor barrier” (BTB) and enhancing the delivery of 60 nm NPs in the tumor region

Summary

Introduction

Ultrasound-mediated delivery of brain-penetrating nanoparticles across the blood-tumor barrier Background/introduction The intact blood-brain barrier (BBB) presents a major obstacle for drug delivery to the brain. Both high interstitial pressure and a nanoporous electrostatically charged tissue composition, produce a “blood-tumor barrier” (BTB), further complicating the treatment of diseases like glioblastoma.

Results

Conclusion