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Pharmaceutics
Special Issues
Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery
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Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 5796

Special Issue Editors

Dr. Manish Ranjan

E-Mail Website
Guest Editor
Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV, USA
Interests: focused ultrasound; blood-brain barrier (BBB); targeted neurotherapeutics; neuromodulation; stereotactic neurosurgery; deep brain stimulation (DBS)
Prof. Dr. Paul Lockman

E-Mail Website
Guest Editor
Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA
Interests: blood-brain barrier; brain metastases; drug delivery; pharmacokinetics
Dr. Tasneem Arsiwala

E-Mail Website
Guest Editor
Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506, USA
Interests: blood-brain barrier; focused ultrasound; disruption; permeability; drug delivery

Special Issue Information

Dear Colleagues,

One of the greatest challenges in the treatment of neurological diseases is the limited delivery of therapeutics to the brain due to the blood–brain barrier (BBB). Recent technological evolution and refinement of focused ultrasound technology provides a novel opportunity to non-invasively disrupt the BBB and allow access to the brain. Current innovative research seeks to fully understand and therapeutically translate this novel modality to improve patient care.

This Special Issue, “Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery”, aims to highlight recent and cutting-edge basic, translational, and clinical work in the field of focused ultrasound-mediated blood–brain barrier disruption and brain therapeutics.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

Basic, translational, and clinical research work on focused ultrasound-mediated blood–brain barrier disruption and drug delivery.

We look forward to receiving your contributions.

Dr. Manish Ranjan
Prof. Dr. Paul Lockman
Dr. Tasneem Arsiwala
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • focused ultrasound
  • blood–brain barrier
  • blood–brain barrier opening/disruption
  • drug delivery
  • targeted therapeutics
  • neurotherapeutics
  • pharmacokinetics
  • immunotherapy
  • microbubbles
  • nanoparticles

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Published Papers (3 papers)

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Research

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15 pages, 7637 KiB  
Article
Protocol to Induce the Temporary Opening of the Blood–Brain Barrier with Short-Time Focused Ultrasound in Rats
by Jorge A. Rodríguez, Mario I. Gutiérrez, Arturo Vera, Daniel A. Hernández, Juan M. Gutiérrez, Daniel Martínez-Fong and Lorenzo Leija
Pharmaceutics 2023, 15(12), 2733; https://doi.org/10.3390/pharmaceutics15122733 - 6 Dec 2023
Cited by 1 | Viewed by 1532
Abstract
Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood–Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching [...] Read more.
Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood–Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB. Full article
(This article belongs to the Special Issue Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery)
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10 pages, 11790 KiB  
Communication
Focused Ultrasound-Mediated Delivery of Anti-Programmed Cell Death-Ligand 1 Antibody to the Brain of a Porcine Model
by Siaka Fadera, Chinwendu Chukwu, Andrew H. Stark, Yimei Yue, Lu Xu, Chih-Yen Chien, Jinyun Yuan and Hong Chen
Pharmaceutics 2023, 15(10), 2479; https://doi.org/10.3390/pharmaceutics15102479 - 17 Oct 2023
Cited by 3 | Viewed by 1968
Abstract
Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body’s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study [...] Read more.
Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by leveraging the body’s immune system to combat cancer cells. However, its effectiveness in brain cancer is hindered by the blood-brain barrier (BBB), impeding the delivery of ICIs to brain tumor cells. This study aimed to assess the safety and feasibility of using focused ultrasound combined with microbubble-mediated BBB opening (FUS-BBBO) to facilitate trans-BBB delivery of an ICI, anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain of a large animal model. In a porcine model, FUS sonication of targeted brain regions was performed after intravenous microbubble injection, which was followed by intravenous administration of aPD-L1 labeled with a near-infrared fluorescent dye. The permeability of the BBB was evaluated using contrast-enhanced MRI in vivo, while fluorescence imaging and histological analysis were conducted on ex vivo pig brains. Results showed a significant 4.8-fold increase in MRI contrast-enhancement volume in FUS-targeted regions compared to nontargeted regions. FUS sonication enhanced aPD-L1 delivery by an average of 2.1-fold, according to fluorescence imaging. In vivo MRI and ex vivo staining revealed that the procedure did not cause significant acute tissue damage. These findings demonstrate that FUS-BBBO offers a noninvasive, localized, and safe delivery approach for ICI delivery in a large animal model, showcasing its potential for clinical translation. Full article
(This article belongs to the Special Issue Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery)
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Review

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13 pages, 635 KiB  
Review
Current Progress in Magnetic Resonance-Guided Focused Ultrasound to Facilitate Drug Delivery across the Blood-Brain Barrier
by Ying Meng, Lorraine V. Kalia, Suneil K. Kalia, Clement Hamani, Yuexi Huang, Kullervo Hynynen, Nir Lipsman and Benjamin Davidson
Pharmaceutics 2024, 16(6), 719; https://doi.org/10.3390/pharmaceutics16060719 - 27 May 2024
Cited by 2 | Viewed by 1589
Abstract
This review discusses the current progress in the clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other ultrasound platforms to transiently permeabilize the blood-brain barrier (BBB) for drug delivery in neurological disorders and neuro-oncology. Safety trials in humans have followed on from [...] Read more.
This review discusses the current progress in the clinical use of magnetic resonance-guided focused ultrasound (MRgFUS) and other ultrasound platforms to transiently permeabilize the blood-brain barrier (BBB) for drug delivery in neurological disorders and neuro-oncology. Safety trials in humans have followed on from extensive pre-clinical studies, demonstrating a reassuring safety profile and paving the way for numerous translational clinical trials in Alzheimer’s disease, Parkinson’s disease, and primary and metastatic brain tumors. Future directions include improving ultrasound delivery devices, exploring alternative delivery approaches such as nanodroplets, and expanding the application to other neurological conditions. Full article
(This article belongs to the Special Issue Ultrasound-Mediated Blood–Brain Barrier Disruption and Drug Delivery)
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