Treatment of Alzheimer's diseases using donepezil nanoemulsion: an intranasal approach.

ABSTRACT

Alzheimer disease (AD) is very common among the older people. There are few medications available as oral and suspension dosage forms for the management of AD. Due to the rising cases of AD and the associated risks of the existing line of treatment, oil in water (o/w) nanoemulsion (NE) loaded with donepezil was prepared to explore intranasal route of administration. The NE was prepared using labrasol (10%), cetyl pyridinium chloride (1% in 80% water), and glycerol (10%), with a drug concentration of 1 mg/ml. The developed NE was characterized for particle size, polydispersity index (PDI), and zeta potential. In vitro release studies were conducted to observe the release of drug. Further in vivo studies of developed NE were done on Sprague Dawley rats using technetium pertechnetate (99mTc) labeled formulations to investigate the nose to brain drug delivery pathway. The nanoemulsion showed particle size of 65.36 nm with a PDI of 0.084 and zeta potential of -10.7 mV. In vitro release studies showed maximum release of 99.22% in 4 h in phosphate-buffered saline, 98% in 2 h in artificial cerebrospinal fluid, and 96% in 2 h in simulated nasal fluid. The cytotoxicity and antioxidant activity of the NE showed dose-dependent cytotoxicity and % radical scavenging activity (%RSA). The images of giemsa staining also confirmed that the developed formulation has no impact on the morphology of cells. Scintigrams showed maximum uptake of NE in the brain. The findings suggested that the developed NE loaded with donepezil hydrochloride could serve as a new approach for the treatment of Alzheimer via nose to brain drug delivery. Graphical abstract.