Use of Biodegradable, Chitosan-Based Nanoparticles in the Treatment of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects more than 24 million people worldwide and represents an immense medical, social and economic burden. While a vast array of active pharmaceutical ingredients (API) is available for the prevention and possibly treatment of AD, applicability is limited by the selective nature of the blood-brain barrier (BBB) as well as by their severe peripheral side effects. A promising solution to these problems is the incorporation of anti-Alzheimer drugs in polymeric nanoparticles (NPs). However, while several polymeric NPs are nontoxic and biocompatible, many of them are not biodegradable and thus not appropriate for CNS-targeting. Among polymeric nanocarriers, chitosan-based NPs emerge as biodegradable yet stable vehicles for the delivery of CNS medications. Furthermore, due to their mucoadhesive character and intrinsic bioactivity, chitosan NPs can not only promote brain penetration of drugs via the olfactory route, but also act as anti-Alzheimer therapeutics themselves. Here we review how chitosan-based NPs could be used to address current challenges in the treatment of AD; with a specific focus on the enhancement of blood-brain barrier penetration of anti-Alzheimer drugs and on the reduction of their peripheral side effects.

Keywords: Alzheimer’s disease; CNS delivery; amyloid-β; biodegradable; blood-brain barrier; chitosan; polymer nanoparticle.

Figure 1

Chemical structure of chitosan.

Scheme 1

The enzymatic degradation of chitosan.

Figure 2

Chemical structure of rivastigmine.

Figure 3

Chemical structure of galantamine.

Figure 4

Chemical structure of tacrine.

Figure 5

Chemical structure of curcumin.

Figure 6

Chemical structure of piperine.

Figure 7

Chemical structure of thymoquinone.

Figure 8

Chemical structure of 17β-estradiol.

Figure 9

Chemical structure of hyaluronic acid.

Figure 10

Chemical structure of methylene blue.

Figure 11

Chemical structure of polysorbate 80.