Liposomes against Alzheimer's Disease: Current Research and Future Prospects

Abstract

Alzheimer's disease, the most common neurodegenerative disease, affects more than 60 million people worldwide, a number that is estimated to double by 2050. Alzheimer's disease is characterized by progressive memory loss, the impairment of behavior, and mood changes, as well as the disturbed daily routine of the patient. Although there are some active molecules that can be beneficial by halting the progression of the disease, the blood-brain barrier and other physiological barriers hinder their delivery and, consequently, the appropriate management of the disease. Therefore, drug delivery systems that effectively target and overcome the blood-brain barrier to reach the targeted brain area would improve treatment effectiveness. Liposomes are lipophilic carriers that consist of a phospholipid bilayer structure, simulating the physiological lipidic layer of the blood-brain barrier and enabling better delivery of the drug to the brain. Given that pure liposomes may have less targeting affinity than functionalized liposomes, modification with groups such as lactoferrin, poly(ethylene glycol), and transferrin may improve specificity. In this mini-review, we summarize the literature on the use of liposomes for the treatment of Alzheimer's disease, focusing on the functionalization moieties of liposomes. In addition, challenges in brain delivery are also discussed.

Keywords: Alzheimer’s disease; brain; functionalization; liposomes; nanoparticles; targeting; therapy.

Figure 1

The number of articles derived from the search for Alzheimer’s disease AND liposomes based on data from (a) PubMed^® and (b) ScienceDirect^®.

Figure 2

Several liposome preparation methods: (a) reverse-phase evaporation method, (b) microfluidic method, and (c) film hydration method.

Figure 3

(a) Structure of glycerolphospholipid. R1 and R2 can be saturated or unsaturated fatty acids, such as decanoic acid, lauric acid, palmitic acid, oleic acid, myristic acid, stearic acid, or erucic acid. R3 can be phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), phosphatidyl serine (PS), phosphatidyl inositol (PI), phosphatidic acid (PA), phosphatidylglycerol (PG), or cardiolipin. (b) Structure of sphingomyelin. (c) Structure of cholesterol. Obtained from Ref. [34].

Figure 4

The structural differences between pure and functionalized liposomes.