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 (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.

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

“…As shown in Scheme , unique nanomaterials have been reported and several nanosized drug delivery systems including liposomes, dendrimers, carbon nanotubes (CNTs), inorganic and hybrid nanoparticles, and polymeric micelles have gained attention and have been tested for targeted drug delivery not only for neurodegenerative diseases but also for several other ailments . The discovery of MCM‐41 was recognized as a major breakthrough in materials science and since then mesoporous silica nanoparticles (MSNs), thanks to their superior physiochemical properties such as large porosity, high surface areas, low toxicity, controllable sizes, and wide range of morphologies compared to conventional nanoparticles (NPs) have emerged as favorable tools in biomedical applications as nanocarriers for encapsulation and delivery of therapeutic medicines .…”

Crossing the Blood-Brain-Barrier: A bifunctional liposome for BDNF gene delivery – A Pilot Study

“…There is evidence for a inverse correlation between BBB penetration and the size of the liposome (Etame et al, 2011;Hanada et al, 2014;Sonavane et al, 2008). The preferred size for brain delivery is 100nm or smaller, but studies have shown that liposomes from 100 to 140 nm have certain advantages, such as a longer half-life in blood circulation and avoidance of plasma proteins (Ross et al, 2018). Moreover, because the BBB is negatively charged, cationic liposomes can trigger cell internalization through electrostatic interactions (Harilal et al, 2020).…”

<p>Recent expansions of novel strategies towards the drug targeting into the brain</p>

“…45,46 Liposome offers site-specific delivery, protects the drug from enzymatic degradation, reduce the adverse effect and represents a biodegradable and biocompatible delivery system which increases both the research and commercial interest for novel drug delivery. [47][48][49] On the other hand, the low encapsulation efficiency and poor stability limit its applicability to some extent. 50 Various investigations, both in the laboratory and commercial scale are under process, utilizes liposome as a potential carrier system for direct nose-to-brain delivery of the drug.…”

“…to assist the drug targeting to the brain. 51 For example; H102 peptide-loaded liposome was developed by Zheng and co-workers 2015 for intranasal delivery to the brain. The brain targeting efficacy of liposome was assessed by estimating the in vivo pharmacokinetic behavior of the drug carrier system.…”