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Clinical translation of nanomedicines for brain diseases: Current challenges and future directions
Abstract
Since the approval of Doxorubicin Liposomal (Doxil®) by the U.S. Food and Drug Administration (FDA) in 1995, the field of nanomedicine has undergone substantial growth, transforming the landscape of drug delivery. Nanomedicine offers innovative approaches to enhance the pharmacokinetics and pharmacodynamics of conventional therapeutic agents. Notably, nanomedicine facilitates targeted and multifunctional drug delivery as well as enabling at-site controlled drug release, improving therapeutic precision and minimizing off-target effects. To date, over 50 nanomedicines have received regulatory approval for the treatment of various diseases, with more than 100 currently undergoing clinical trials. However, despite these great advancements, the application of nanomedicines in treating brain diseases remains limited. The blood-brain barrier (BBB) hurdle and the intricate complexity of the central nervous system (CNS) significantly hinder the development of brain-targeted nanotherapeutics. In this review, we will summarize the current challenges encountered in developing nanomedicines for brain diseases and explore potential strategies to overcome these barriers, aiming to accelerate their translation into clinical practice.
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“The majority of clinical trials, in addition to being in early phases, are primarily focused on brain tumors, since NDs like AD express multiple and often interrelated pathogenic pathways hindering the discovery of universal therapeutic targets [127].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [127]
In the citing paper
“Their potential is confirmed by the fact that they are the only ones that received approval for human use [127].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [127]
In the citing paper
“Although the approval of over 50 NP-based therapies has occurred, only one is specifically brain-targeted (NanoTherm®, a magnetic-nanoparticle-based therapy intended for use in brain cancer), underscoring the struggle for effective clinical translation within this domain.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [127]
In the citing paper
“While essential to observe their effects in a living organism and study its pharmacokinetics, in vivo studies are robust and must be consistent and independent from interspecies variability [127].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [127]
In the citing paper
“Other limitations include off-target effects because of drug interaction with unwanted cells, disease heterogeneity demanding biomarker-driven patient classification for a personalized therapy, regulations, pricing, social considerations, and so on [127,129].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [127]
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Metadata
- Authors
- Wang, G., Wang, N., Xia, X., Ismail, M., & Shi, B.
- Affiliations
- Macquarie University (AU)
- Henan University (CN)
- University of Technology Sydney (AU)
- Corresponding author
- Ismail, Muhammad
- Shi, Bingyang
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2026-01
- Volume
- 389
- Pages
- 114426
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4416416234
- Cited by
- 33
- References
- 409
- Citations by year
- 2026: 33
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Institute NSW (2022/ECF1449)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- nanomedicine, brain disorders, blood-brain barrier, brain drug delivery, nanotherapeutics, clinical translation, central nervous system, controlled drug release, targeted drug delivery
- MeSH terms
- Animals, Blood-Brain Barrier, Brain Diseases, Humans, Drug Delivery Systems, Nanomedicine, Nanoparticles
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