Nanostructured Lipid Carriers of Donepezil Hydrochloride for the Treatment of Alzheimer's Disease.

BACKGROUND

Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriate concentration in the brain cells, its efficacy upon oral administration is limited, and thus investigation of alternative administration route is necessary.

OBJECTIVE

The objective of this study was to develop donepezil HCl-loaded Nanostructured Lipid Carriers (NLCs) that can bypass the blood-brain barrier and thus be directly delivered to the brain through the nasal route. This method improves availability at the site of action, reduces the negative effects of oral medication, and ensures an expedited commencement of action.

METHODS

High-pressure homogenization and ultrasonication were used to formulate NLCs. Glyceryl Monostearate (GMS) as a solid lipid, Tween 80 as a surfactant, and Poloxamer 407 as a cosurfactant were used. In this study, argan oil was employed as a liquid lipid as well as a penetration enhancer.

RESULTS

The chosen NLCs displayed a particle size of 137.34 ± 0.79 nm, a PDI of 0.365 ± 0.03, and a zeta potential of -10.4 mV. The selected formulation showed an entrapment efficiency of 84.05 ± 1.30% and a drug content of 77.02 ± 0.23%. The concentration of the drug in the brain after intravenous and intranasal administration of DNZ NLCs at 1 h was found to be 0.490 ± 0.007 and 4.287 ± 0.115, respectively. Thus, the concentration of DNZ achieved in the brain after intranasal administration of DNZ NLCs was approximately 9 times more than the concentration when administered by intravenous route.

CONCLUSION

The DNZ-loaded NLCs, when administered via nasal route, showed markedly improved drug availability in the brain, suggesting an efficient drug delivery strategy to treat Alzheimer's disease.