Final published version, 3.81 MB, PDF document
Available under license: CC BY-NC
Final published version
Licence: CC BY-NC
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Liposome delivery systems for the treatment of Alzheimer’s disease
AU - Ross, Callum
AU - Taylor, Mark Neville
AU - Fullwood, Nigel James
AU - Allsop, David
PY - 2018/12/12
Y1 - 2018/12/12
N2 - Alzheimer’s disease (AD) will affect around 115 million people worldwide by the year 2050. It is associated with the accumulation of misfolded and aggregated proteins (β-amyloid and tau) in the senile plaques and neurofibrillary tangles found in the brain. Currently available drugs for AD only temporarily alleviate symptoms and do not slow the inevitable progression of this disease. New drugs are required that act on key pathologies in order to arrest or reverse cognitive decline. However, there has been a spectacular failure rate in clinical trials of conventional small molecule drugs or biological agents. Targeted nanoliposomes represent a viable and promising drug delivery system for AD that have not yet reached clinical trials. They are biocompatible, highly flexible, and have the potential to carry many different types of therapeutic molecules across the blood–brain barrier (BBB) and into brain cells. They can be tailored to extend blood circulation time and can be directed against individual or multiple pathological targets. Modifications so far have included the use of brain-penetrating peptides, together with Aβ-targeting ligands, such as phosphatidic acid, curcumin, and a retro-inverted peptide that inhibits Aβ aggregation. Combining several modifications together into multifunctional liposomes is currently a research area of great interest. This review focuses on recent liposomal approaches to AD therapy, including mechanisms involved in facilitating their passage across the BBB, and the evaluation of new therapeutic agents for blocking Aβ and/or tau aggregation.
AB - Alzheimer’s disease (AD) will affect around 115 million people worldwide by the year 2050. It is associated with the accumulation of misfolded and aggregated proteins (β-amyloid and tau) in the senile plaques and neurofibrillary tangles found in the brain. Currently available drugs for AD only temporarily alleviate symptoms and do not slow the inevitable progression of this disease. New drugs are required that act on key pathologies in order to arrest or reverse cognitive decline. However, there has been a spectacular failure rate in clinical trials of conventional small molecule drugs or biological agents. Targeted nanoliposomes represent a viable and promising drug delivery system for AD that have not yet reached clinical trials. They are biocompatible, highly flexible, and have the potential to carry many different types of therapeutic molecules across the blood–brain barrier (BBB) and into brain cells. They can be tailored to extend blood circulation time and can be directed against individual or multiple pathological targets. Modifications so far have included the use of brain-penetrating peptides, together with Aβ-targeting ligands, such as phosphatidic acid, curcumin, and a retro-inverted peptide that inhibits Aβ aggregation. Combining several modifications together into multifunctional liposomes is currently a research area of great interest. This review focuses on recent liposomal approaches to AD therapy, including mechanisms involved in facilitating their passage across the BBB, and the evaluation of new therapeutic agents for blocking Aβ and/or tau aggregation.
KW - amyloid
KW - blood–brain barrier
KW - cell-penetrating peptides
KW - neurofibrillary tangles
KW - senile plaques
KW - tau
U2 - 10.2147/IJN.S183117
DO - 10.2147/IJN.S183117
M3 - Journal article
VL - 2018
SP - 8507
EP - 8522
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
SN - 1178-2013
IS - 13
ER -