Review Article
Translational Strategies for Blood-Brain Barrier Penetration and Targeted Central Nervous System Drug Delivery
Arunima Ghosh
,
Sourav Dutta*
Issue:
Volume 11, Issue 2, June 2026
Pages:
26-35
Received:
13 April 2026
Accepted:
23 April 2026
Published:
11 May 2026
DOI:
10.11648/j.bmb.20261102.11
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Abstract: The blood-brain barrier (BBB) is a highly selective semi-permeable interface that maintains central nervous system (CNS) homeostasis by tightly regulating the passage of substances from systemic circulation into the brain. While essential for neuroprotection, this barrier presents the foremost challenge in neuropharmacology, effectively excluding the vast majority of small-molecule drugs and nearly all large-molecule biopharmaceuticals from reaching therapeutic targets within the CNS. Diseases such as glioblastoma, Alzheimer's disease, Parkinson's disease, and a broad spectrum of neurological disorders therefore remain difficult to treat despite considerable advances in drug development. This review aims to provide a comprehensive and critically evaluated combination of current and emerging strategies for CNS drug delivery, mapping the translational landscape from experimental methodologies to clinical application, with particular attention to advances reported in 2025 and 2026. The review systematically examines both non-invasive and invasive approaches to overcoming the BBB. Non-invasive strategies include carrier-mediated transport, receptor-mediated transcytosis (RMT), peptide-based delivery systems incorporating cell-penetrating and receptor-targeting peptides, and nanotechnology-based therapeutics such as lipid nanoparticles, polymeric nanocarriers, and exosome-based platforms. Among invasive physical disruption methods, microbubble-enhanced focused ultrasound (MB-FUS) and convection-enhanced delivery are evaluated for their clinical utility and safety profiles. The integration of peptide-based systems with nanocarriers is highlighted as a particularly modular and scalable strategy for targeted CNS pharmacotherapy. Clinical trial data from 2025 and 2026 are incorporated to contextualize these strategies within real-world therapeutic outcomes, including demonstrated survival benefits in glioblastoma patients and accelerated amyloid clearance in Alzheimer's disease. The review further discusses the emerging role of artificial intelligence in enabling precision neuro-nanomedicine, from target identification to personalized dosing optimization, alongside the evolving regulatory landscape governing CNS drug delivery technologies. This review provides a forward-looking roadmap for the clinical translation of targeted CNS pharmacotherapy, underscoring the necessity of interdisciplinary collaboration among neuroscience, nanotechnology, neuropharmacology, and regulatory science to overcome the persistent challenge posed by the blood-brain barrier (BBB).
Abstract: The blood-brain barrier (BBB) is a highly selective semi-permeable interface that maintains central nervous system (CNS) homeostasis by tightly regulating the passage of substances from systemic circulation into the brain. While essential for neuroprotection, this barrier presents the foremost challenge in neuropharmacology, effectively excluding t...
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