Overcoming the Blood-Brain Barrier for Drug Delivery to the Brain.
Authors: Katz JS, Slika H, Sattari SA, Malla AP, Xia Y, Antar A, Ran K, Tyler B
The blood-brain barrier (BBB) greatly hinders the delivery of therapeutic agents to the brain. Vast efforts have been dedicated to exploring novel strategies and developing technologies to enhance the delivery of drugs, nucleic acids, antibodies, etc., effectively in the context of brain tumors, neurodegenerative diseases, and other brain pathologies. These strategies aim to guarantee impactful and targeted accumulation of the delivered agents within the brain or within specific areas or niches through either localized sustained delivery (convection-enhanced delivery and implantable biodegradable polymer-based systems), encapsulation of the agents within vectors that can enhance their ability to penetrate the BBB and achieve proper interstitial distribution (viral vectors, exosomes, and nanoparticles), or modulation of the BBB to facilitate the crossing of the delivered cargo (focused ultrasound and receptor/transporter-mediated delivery). Indeed, exploring these innovative strategies and how they may work synergistically with conventional treatments is crucial to advancing the management of brain pathologies.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review and summarize evolving strategies to overcome the blood-brain barrier and enhance delivery of therapeutic agents to the brain.
Animal model / Human subject
Not reported in the provided text.
Disease model
brain tumors, neurodegenerative diseases, and other brain pathologies
MRI or image guidance method
Not specified in the provided text
Targeted brain region(s)
Not Specified
Target coordinates
not reported
Cargo name and characteristics
Small-molecule drugs (pharmacologic compounds), nucleic acids (therapeutic RNA/DNA for gene therapy, siRNA, mRNA), antibodies (therapeutic proteins), viral vectors (e.g., AAV or other viral delivery vehicles), exosomes (biological nanovesicles), synthetic nanoparticles (engineered nanocarriers)
Route of administration
Intranasal and intravenous
Outcomes and Safety
Summary of Outcomes
Various delivery strategies (convection-enhanced delivery, implantable biodegradable polymers, exosomes, AAV vectors, focused ultrasound, intranasal delivery, and nanoparticles) enhance crossing of the blood–brain barrier and targeted accumulation of therapeutic agents in the brain, potentially improving treatment efficacy for brain tumors and neurodegenerative diseases.
Duration of biological effect
not specified
Safety-related matter
Clinical studies have supported the safety of focused ultrasound (FUS)-mediated BBB opening and amyloid plaque reduction in AD, but randomized controlled trials are still needed to establish the safety, feasibility, and efficacy of transnasal delivery and other BBB-targeting strategies.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Not specified
FUS Frequency
Not specified
FUS Intensity
Not reported
FUS Pressure
Not reported
FUS Mode
not specified
Pulse duration
Not reported
Duration of a single FUS session
Not reported in the provided text
Focal Characteristics
not provided
Treatment frequency
Not specified
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