Table 1.

Nanoparticle strategies for the delivery of statins to the atherosclerotic plaque.

Therapeutic Agent	Type of nanoparticle	Key nanoparticle materials	Size/Charge	Loading capacity (LC) and loading efficiency (LE)	Route of delivery	Injected dose	Animal model	Targeting strategy	Key Findings	Ref
Pitavastatin (lipophilic)	Polymeric Nanoparticle	PLGA	159 nm/-4mV	LC = 12.0% (w/v)	IV injection	Weekly injection of 0.012 mg of pitavastatin for 4 weeks	ApoE−/− mice	N/A NP uptake by macrophages	34% decreased plaque area in treatment compared to control	[84]
Atorvastatin (lipophilic)	Polymeric Nanoparticle	amphiphilic oxidation sensitive chitosan oligosaccharide	∼207 nm/∼-26 mV	LE = 48.3% LC = 5.1%	IV injection	5 x 107 cells with NP internalised at an efficiency of ∼14.7%, injected weekly for 9 weeks	ApoE−/− mice	Macrophage membrane coating to prevent the clearance of the NPs from RES.	Decreased plaque area of ∼8% in MM-AT-NP compared to the saline group which had ∼20% plaque area of the total aorta tissue area	[85]
	Core/shell Nanoparticle	Core: hydrophobic statin aggregate Shell: Hyaluronic acid	122 nm/−35 mV (water) 135nm/−17 mV (PBS)	LC = 35%	IV injection	8.5 mg atorvastatin per kg animal body weight administered every other day, total 4 doses	ApoE−/− mice	Hylaluronic acid (HA) targeting the CD44 receptors in atherosclerotic plaque	Total plaque area in treatment group was 69% less than the control group	[86]
Simvastatin (lipophilic)	Liposome	DSPC DSPE-PEG2000	208.90 ± 3.99nm/−20 mV	LE = 93.57 ± 1.28% LC = 43.39 ± 7.6%	IV injection	10 mg/kg of simvastatin, 1 mg/kg epigallocatechin gallate (EGCG) twice a week for 3 weeks	ApoE−/− mice	N/A	SE-LNP treatment significantly reduced total aortic plaque area (<10%) compared to model (∼28%)	[87]
	Reconstituted HDL nanoparticle	rHDL	25–30 nm	LE = N/A LC = 11.6% (w/v)	IV injection	15 mg/kg of statin in rHDL bi-weekly for 12 weeks	ApoE−/− mice	N/A	31% decrease in total plaque area compared to the model group	[88]
		rHDL	138.2 ± 2.7 nm/-28.38 ± 0.52 mV	LE = 90.64 ± 0.43% LC = 5.03 ± 0.32%	IV injection	0.4 mg/kg every other day for 8 weeks	Male NZ white rabbits	Hylaluronic acid (HA) targeting the CD44 receptors in atherosclerotic plaque	Lesion positive staining showed a 10.9% lesion area of the treatment group compared to the 86.8% lesion area present in the model group	[89]
	Core/shell nanoparticle	Core: cyclodextrin/statin complex Shell: phospholipid	104 ± 13 nm/−20 ± 0.8 mV	N/A	IV injection	15 mg/kg of statin and 100 mg/kg of cyclodextrin 2,5, 8 and 11 days after LCA ligation	ApoE−/− mice	N/A	∼76% reduction in total plaque area in the treatment group compared to the control group	[90]
	Polymeric Nanoparticle	amphiphilic diblock copolymer (PEG-Ptyr-EO)	131.5 ± 6.4 nm/38.4 ± 9.7 mV	LE = 84.3% LC = 7.3%	IV injection	30 mg/kg of statin once a week for 4 weeks	ApoE−/− mice	Hylaluronic acid (HA) targeting the CD44 receptors	∼50% decrease in plaque area in the treatment group compared to control group	[91]
Lovastatin (lipophilic)	Reconstituted HDL nanoparticle	rHDL	152.9 ± 2.4 nm/-25.66 ± 0.65 mV	LE = 90.21 ± 0.50% LC = 4.34 ± 0.59%	IV injection	0.4 mg/kg, every other day for 8 weeks	Male NZ white rabbits	Hylaluronic acid (HA) targeting the CD44 receptors	Lesion positive staining showed an approximate 82% decrease in lesion area in treatment group compared to the model group	[92]
Rosuvastatin (RSV) (hydrophilic)	Mesoporous silica nanoparticles	Silica	137.5 nm /−16.3 mV	LE = 48.15 ± 0.95% LC = 8.78 ± 0.16%	IV injection	10 mg/kg for statin and 1.25 mg/kg for anti-CD9, injected every 2 days for a total of 8 doses	ApoE−/− mice	Anti-CD9 antibody targeting CD9 present in macrophages in the plaque environment	10.96% and 23.99% decrease of blood cholesterol level compared to free drug and control (PBS) respectively Treatment group had a lower plaque burden (7.5%) compared to the model group (13.3%)	[93]