Challenges and opportunities in CNS delivery of therapeutics for neurodegenerative diseases
Abstract
With an increase in lifespan and changing population demographics, the incidence of central nervous system (CNS) diseases is expected to increase significantly in the 21st century. The most challenging of the CNS diseases are neurodegenerative diseases, characterized by age-related gradual decline in neurological function, often accompanied by neuronal death. Alzheimer's disease, Parkinson's disease and Huntington's disease are some examples of neurodegenerative diseases and have been well described in terms of disease mechanisms and pathology. However, successful treatment strategies for neurodegenerative diseases have so far been limited. Delivery of drugs into the CNS is one of the most challenging problems faced in the treatment of neurodegeneration. In this review, we describe the difficulties with CNS therapy, especially with the use of biological macromolecules, such as proteins and nucleic acid constructs. CNS therapeutics also represents a huge opportunity and examples of strategies that can enhance therapeutic delivery for the treatment of neurodegenerative diseases are emphasized. It is anticipated that with an increase in biological understanding of neurodegenerative diseases, there will be even more therapeutic opportunities. As such, these delivery strategies have a very important role to play in the future in the translation of CNS therapeutics from bench to bedside.
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Treatment of central nervous system diseases is severely constrained by the blood-brain barrier.
“The treatment of central nervous system (CNS) diseases, such as neurodegenerative disorders, brain tumors, brain infections, and stroke, is severely constrained by the blood-brain barrier (BBB) because it prevents the transfer of most of small-molecule drugs and macromolecules (e.g., peptides, gene drugs, and protein drugs) into the brain (1–6).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [2]
The blood-brain barrier prevents the transfer of most small-molecule drugs and macromolecules into the brain.
“it prevents the transfer of most of small-molecule drugs and macromolecules (e.g., peptides, gene drugs, and protein drugs) into the brain (1–6).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [2]
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- Authors
- Barchet, T. M., & Amiji, M. M.
- Affiliations
- Northeastern University (US)
- ORCID
- Amiji, Mansoor M
- Venue
- Expert Opinion on Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2009-03
- Volume
- 6
- Issue
- 3
- Pages
- 211-225
- ISSN
- 1742-5247 (ISSN-L)
- 1744-7593
- OpenAlex
- W2072970553
- Cited by
- 145
- References
- 8
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 21 · 2023: 9 · 2022: 23 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 8
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- brain drug delivery, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Huntington's disease, biological macromolecules, therapeutic proteins, nucleic acid therapeutics, neuronal cell death
- MeSH terms
- Animals, Blood-Brain Barrier, Central Nervous System, Drug Administration Routes, Drug Carriers, Humans, Drug Delivery Systems, Neuroprotective Agents, Neurodegenerative Diseases, Nanotechnology
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