Dataset Information

Liposome delivery systems for the treatment of Alzheimer's disease.

ABSTRACT: 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 (?-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 A?-targeting ligands, such as phosphatidic acid, curcumin, and a retro-inverted peptide that inhibits A? 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 A? and/or tau aggregation.

SUBMITTER: Ross C

PROVIDER: S-EPMC6296687 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Liposome delivery systems for the treatment of Alzheimer's disease.

Ross Callum C Taylor Mark M Fullwood Nigel N Allsop David D

International journal of nanomedicine 20181212

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 ...[more]

PMID: 30587974

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Project description:Alzheimer's disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions. Alzheimer's disease is associated with dementia and a progressive decline in memory, thinking, and social skills, eventually leading to a point that the individual can no longer perform daily activities independently. Currently available drugs on the market temporarily alleviate the symptoms, however, they are not successful in slowing down the progression of Alzheimer's disease. Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier. Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications. Recently, liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier. Liposomes are being used as a component of nanoparticle drug delivery; due to their biocompatible nature; and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells. Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders. The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment. Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer's disease. This review deals with Alzheimer's disease and emphasize on challenges associated with drug delivery to the brain, and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer's disease. This review also sheds some light on variation of liposomes. Additionally, it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer's disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer's disease.

Project description:Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has also been implicated in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), and secondary injury following intracerebral hemorrhage (ICH). Chelation of brain iron is thus a promising therapeutic strategy for improving behavioral outcomes and slowing neurodegeneration in the aforementioned disease states, though the effectiveness of DFO treatment is limited on several accounts. Systemically administered DFO results in nonspecific toxicity at high doses, and the drug's short half-life leads to low patient compliance. Mixed reports of DFO's ability to cross the blood-brain barrier (BBB) also appear in literature. These limitations necessitate novel DFO formulations prior to the drug's widespread use in managing neurodegeneration. Herein, we discuss the various dosing regimens and formulations employed in intranasal (IN) or systemic DFO treatment, as well as the physiological and behavioral outcomes observed in animal models of AD, PD, and ICH. The clinical progress of chelation therapy with DFO in managing neurodegeneration is also evaluated. Finally, the elimination of intranasally administered particles via the glymphatic system and efflux transporters is discussed. Abundant preclinical evidence suggests that intranasal DFO treatment improves memory retention and behavioral outcome in rodent models of AD, PD, and ICH. Several other biochemical and physiological metrics, such as tau phosphorylation, the survival of tyrosine hydroxylase-positive neurons, and infarct volume, are also positively affected by intranasal DFO treatment. However, dosing regimens are inconsistent across studies, and little is known about brain DFO concentration following treatment. Systemic DFO treatment yields similar results, and some complex formulations have been developed to improve permeability across the BBB. However, despite the success in preclinical models, clinical translation is limited with most clinical evidence investigating DFO treatment in ICH patients, where high-dose treatment has proven dangerous and dosing regimens are not consistent across studies. DFO is a strong drug candidate for managing neurodegeneration in the aging population, but before it can be routinely implemented as a therapeutic agent, dosing regimens must be standardized, and brain DFO content following drug administration must be understood and controlled via novel formulations.

Dataset Information

Liposome delivery systems for the treatment of Alzheimer's disease.

Publications

Liposome delivery systems for the treatment of Alzheimer's disease.

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