Advances and challenges in novel drug delivery systems for glioma therapy.
Authors: Ma P, Li Y, Gu Y, Zeng H, Xiang H, Cao Z, Han Y, Cui Y, Liu H
Glioma therapy faces substantial challenges primarily due to the restrictive nature of the blood-brain barrier (BBB), limiting effective drug penetration and reducing therapeutic efficacy. Recent advancements in novel drug delivery systems (DDS), including exosome-mediated carriers, drug conjugates, and ultrasound-assisted delivery, have demonstrated promising results in overcoming these limitations. Exosomes offer superior biocompatibility, efficient BBB crossing, and natural cellular targeting capabilities; drug conjugates enable highly selective drug delivery through tumor-specific ligands; and ultrasound-assisted systems transiently disrupt the BBB to permit greater drug entry. Despite encouraging preclinical and early clinical outcomes, significant translational barriers remain. Challenges such as exosome manufacturing scalability, conjugate stability, and immunogenicity, as well as the optimization of ultrasound protocols, must be thoroughly addressed to achieve clinical translation. Overcoming these hurdles requires ongoing multidisciplinary collaboration and rigorous clinical evaluation. Continued progress in refining these innovative DDS approaches holds the potential to markedly improve therapeutic outcomes and patient prognosis in glioma treatment.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To review recent advances in novel drug delivery systems—exosome-mediated carriers, drug conjugates, and ultrasound-assisted delivery—for overcoming the blood–brain barrier in glioma therapy and to discuss the translational challenges to clinical application.
Animal model / Human subject
Not specified in the provided text.
Disease model
glioma
MRI or image guidance method
Not specified in the provided text
Targeted brain region(s)
Not Specified In The Provided Text
Target coordinates
Not provided
Cargo name and characteristics
Exosome-mediated carriers — natural extracellular vesicles (nanoparticle-like biological vesicles) used as delivery vehicles with high biocompatibility, efficient BBB crossing and inherent cellular/tumor-targeting properties; Drug conjugates — small-molecule therapeutics chemically linked to tumor-specific ligands (targeted small-molecule conjugates) designed for selective delivery to glioma cells (issues noted: conjugate stability and potential immunogenicity).
Route of administration
Not explicitly stated in the text; delivery approaches described include exosome-mediated carriers, tumor-targeted drug conjugates, and ultrasound-assisted transient disruption of the blood–brain barrier to enable drug entry.
Outcomes and Safety
Summary of Outcomes
Exosome-based carriers, tumor-specific drug conjugates, and ultrasound-assisted delivery enhance drug crossing of the blood–brain barrier and tumor targeting, improving therapeutic efficacy against glioma in preclinical and early clinical studies.
Duration of biological effect
not specified
Safety-related matter
The paper notes potential safety concerns including immunogenicity of exosomes/conjugates and risks from transient BBB disruption by ultrasound that require optimization and rigorous clinical evaluation.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Not specified
FUS Frequency
Not reported in the provided text
FUS Intensity
Not reported
FUS Pressure
Not reported
FUS Mode
not specified
Pulse duration
Not reported in the provided text
Duration of a single FUS session
Not reported in the provided text
Focal Characteristics
Enhancing BBB penetration for glioma treatment using exosome-mediated carriers, drug conjugates, and ultrasound-assisted delivery.
Treatment frequency
not specified
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