Biomaterials for the Treatment of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) as a progressive and fatal neurodegenerative disease represents a huge unmet need for treatment. The low efficacy of current treatment methods is not only due to low drug potency but also due to the presence of various obstacles in the delivery routes. One of the main barriers is the blood–brain barrier. The increasing prevalence of AD and the low efficacy of current therapies have increased the amount of research on unraveling of disease pathways and development of treatment strategies. One of the interesting areas for the latter subject is biomaterials and their applications. This interest originates from the fact that biomaterials are very useful for the delivery of therapeutic agents, such as drugs, proteins, and/or cells, in order to treat diseases and regenerate tissues. Recently, manufacturing of nano-sized delivery systems has increased the efficacy and delivery potential of biomaterials. In this article, we review the latest developments with regard to the use of biomaterials for the treatment of AD, including nanoparticles and liposomes for delivery of therapeutic compounds and scaffolds for cell delivery strategies.

Recent Status of Nanomaterial Fabrication and Their Potential Applications in Neurological Disease Management

“…This protein also has a risk factor for the growth of mild cognitive impairment (MCI) which may later convert to AD development [ 29 ]. AD contributes in more than 80% of dementia and now it has been categorized as the most devastating disease in the world [ 20 , 30 – 32 ]. Environmental pollution is the major cause of AD and PD progression.…”

“…Present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations Hadavi and Poot [ 32 ] Gregori et al [ 104 ] Wen et al [ 105 ] Sercombe et al [ 106 ] Solid lipid NPs and lipid-coated microbubble/NP-derived (LCM/ND) 50–1000 nm Piperine, galantamine, lipoyl-memantine, rivastigmine HCl Stabilizing drugs that suffer from physicochemical or biological instability; improving the bioavailability of drugs that cross the BBB; increasing permeating of drugs through the BBB Wen et al [ 105 ] Qu et al [ 107 ] D’Arrigo [ 108 ] Chitosan NPs 15–200 nm Tacrine, Aβ fragment, Enhanced concentration of drug in the brain, more stable, permeable, and bioactive Sahni et al [ 103 ] Gregori et al [ 104 ] Wen et al [ 105 ] Ahmed et al [ 109 ] Magnetite NPs 1 nm to 5 μm Tacrine Useful as selective biomarkers for detecting the location and the removal of other amyloid plaques derived from different amyloidogenic proteins Sahni et al [ 103 ] Gregori et al [ 104 ] Busquets et al [ 110 ] Sara Teller et al [ 111 ] Chen et al [ 112 ] Albumin NPs 40–500 nm Apo-E binding, tacrine Enhanced brain uptake of NPs by cerebral endothelium, by an endocytic mechanism, followed by transcytosis into the brain parenchyma Sahni et al [ 103 ] Gregori et al [ 104 ] Saraiva et al [ 113 ] Karimi et al [ 114 ] Gold NPs 1–150 nm Aβ-binding peptide The prepared NPs dissolve toxic protein deposits of Aβ1–42 (amyloid deposits) by the combined use of weak microwave fields ...…”

“…They can be strategically engineered to carry drugs and possess a suitable half-life for many diseases Gregori et al [ 104 ] Sarko et al [ 116 ] Quek et al [ 117 ] Chen et al [ 118 ] Jiang and Gao [ 119 ] Polystyrene NPs 240 nm Penicillamine Deliver D-penicillamine to the brain for the prevention of Aβ accumulation Hadavi and Poot [ 32 ] Sahni et al [ 103 ] Saraiva et al [ 113 ] Core–shell NPs – Thioflavin T and S Tools to trace and clear Aβ in the brain Sahni et al [ 103 ] Busquets et al [ 110 ] Sonmez et al [ 120 ] Nanolipidic and microparticles 30–80 nm Polyphenol EGCG, donepezil Prevent Aβ formation. Acetylcholine esterase inhibitor with high specificity for acetylcholine esterase in the central nervous system Hadavi and Poot [ 32 ] Sahni et al [ 103 ] Trimethylated chitosan conjugated-PLGA NPs 94 ± 8.1 to 146.5 ± 5.1 Coenzyme Q10(Co-Q10) Q10-loaded TMC/PLGA–NP greatly improved memory impairment and restoring it to a normal level Sahni et al [ 103 ] Poly(butyl) cyanoacrylate NPs 178 ± 0.59 to 197 ± 2.3 Apo-E binding Attachment of ApoE3 to C-PBCA NPs increased the uptake of curcumin into cells as compared to the plain solution or untargeted NPs Sahni et al [ 103 ] Nanoemulsions 10–1000 nm Nano-PSO, lipid-coated microbubble/NP-derived (LCM/ND)-scavenger receptor class B type I Good solubilization and protection of lipophilic drugs in the oil droplets and easy for large-scale production Wen et al [ 105 ] Mizrahi et al [ 121 ] Microemulsions 1–100 nm Huperzine A and lig...…”

“…nanocarriers and strong conjugation of valuable drug compounds to the vectors having active transport capacity of drugs through BBB in the brain. Several NMs are produced using nanotechnology that can deliver desirable therapeutic compounds into the brain tissues as well as near the site of drug action in other tissues [ 32 , 50 , 51 , 156 ]. Biodegradable materials as a carrier also revealed an effective drug delivery near the site of action.…”

“…These NMs have additional properties as their surface can be manipulated and or engineered with hydrophilic polyethylene glycol layer allowing to protect the drugs from enzymatic degradation and recognition by the immune system [ 157 ]. Thus, these significant features enable those compounds to be considered as promising vehicle for AD and other neurological disease diagnosis and treatment [ 32 ].…”