Table 4 Selected relevant pre-clinical studies based on recent PNPs for the diagnosis and treatment of AD

Lutein

PLGA

Chitosan

0–20 mM

Incubation

SHSY-5Y cells

RPMI 2650 cells

NPs are highly deposited in brain following i.n. route and demonstrated to possess significant ROS scavenging activity

Dhas et al. [174]

4 mg LT/kg

i.n

Sprague Dawley rats

NAP

PLA

TPL

PEG

10 μM

Incubation

bEnd.3 cells

PC12 cells

HT22 cells

CTX-TNA2 cells

TPL-PNPs show higher binding affinity to either GT1b ganglioside receptor or brain capillary endothelial bEnd.3 cells, increase the BBB-penetration and neuron-targeting efficacy, enhance ROS scavenging ability and protect microtubule from Aβ25‐35-induced neurotoxicity, inhibit okadaic acid-induced tau aggregation and neuronal apoptosis, improve the cognitive performance of treated mice, down-regulate the tau phosphorylation level, promote axonal transport and attenuate microgliosis

Guo et al. [185]

6–24 μg NPs/kg/day

N.A

ICR mice

CDs

GMP

Chitosan

Eu(NO3)3

CuCl2

0.67 mg/ml

NPs-CSF sample

incubation

AD rats

Developed NPs act as a ratiometric fluorescent probe for the detection of Aβ monomers. In CSF and various brain tissues of rats, developed NPs are able to recognize the Aβ peptide and fluoresce, thus leading to its detection and quantification

Liu et al. [181]

Phytol

PLGA

–

5–10 µg/ml

Incubation

Neuro-2a cells

PNPs increase the lifespan, chemotaxis behaviour and decrease Aβ deposition and ROS production in the in vivo models of AD. Moreover, PNPs treatment downregulate the expression of AD associated genes viz Aβ, ace-1 and hsp-4 upregulate the gene dnj-14, involved in the longevity of nematodes, and reduce the expression of Aβ peptide at the protein level

Sathya et al. [176]

25, 50 and 100 μg/ml

Exposition

Caenorhabditis elegans (CL2006, CL4176)

Curcumin

PLGA

[Gd]DTPA

Chitosan

IgG4.1

K16ApoE

100 µCi/100 µL

i.v

Tg2576 mice

NPs improve BBB transcytosis by coating with a K16ApoE

NPs enhance MRI contrast to detect Aβ plaques

Ahlschwede et al. [180]

EGCG/AA

PLGA

PEG

15–500 μg/ml

Incubation

BMVECs

NPs effectively penetrate through the in vitro BBB without damaging the BBB integrity. NPs treatment reduce neuroinflammation, Aβ plaque burden, soluble and insoluble Aβ42 peptide levels

and enhance synapsis expression, spatial learning and memory processes

Cano et al. [178]

40 mg/kg/day

v.o

APP/PS1 mice

DBP

PLGA

–

2.5 mg/kg

i.v

5XFAD mice

Inhibition Aβ aggregation in vitro. Attenuation of Aβ accumulation, neuroinflammation, neuronal loss and cognitive dysfunction

Jeon et al. [182]