» Articles » PMID: 38551038

Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein- mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

References
1.
Caselli R, Reiman E . Characterizing the preclinical stages of Alzheimer's disease and the prospect of presymptomatic intervention. J Alzheimers Dis. 2012; 33 Suppl 1:S405-16. PMC: 3628721. DOI: 10.3233/JAD-2012-129026. View

2.
Citron M, Oltersdorf T, Haass C, McConlogue L, Hung A, Seubert P . Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature. 1992; 360(6405):672-4. DOI: 10.1038/360672a0. View

3.
Abbas M . Potential Role of Nanoparticles in Treating the Accumulation of Amyloid-Beta Peptide in Alzheimer's Patients. Polymers (Basel). 2021; 13(7). PMC: 8036916. DOI: 10.3390/polym13071051. View

4.
Ferri C, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M . Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366(9503):2112-7. PMC: 2850264. DOI: 10.1016/S0140-6736(05)67889-0. View

5.
Barnes D, Yaffe K . The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurol. 2011; 10(9):819-28. PMC: 3647614. DOI: 10.1016/S1474-4422(11)70072-2. View