Table 4.

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

Loaded molecule	Polymeric matrix	Surface modifications	Dose	Admin. route	In vitro/in vivo model	Results	Refs
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]

AA, ascorbic acid; BMVECs, brain microvascular endothelial cells; CDs, carbon dots; CSF, cerebrospinal fluid; DBP, Vitamin D-binding protein; EGCG; Epigallocatechin-3-gallate; GMP, guanosine monophosphate disodium; NAP, neuroprotective peptide; ROS, Reactive oxygen species; TPL, fusion peptide comprising a BBB-penetrating peptide TGN and a neuron binding peptide Tet1