Design and development of donepezil hydrochloride loaded nanostructured lipid carriers for efficient management of Alzheimer's disease

Abstract

Objective: The primary objective of this study was to develop nanostructured lipid carriers of donepezil hydrochloride (DNZ HCl) for effective management of Alzheimer's disease (AD).

Significance: Intranasal administration of DNZ NLC containing Nigella sativa (NS) oil as a liquid lipid may significantly improve nasal penetration and deliver the drug directly to the brain avoiding blood brain barrier (BBB).

Method: High pressure homogenization was used to prepare nanostructured lipid carriers (NLCs), followed by ultrasonication. Glyceryl monostearate (GMS), Tween 80, and Poloxamer 407 were used as solid lipid, surfactant and co-surfactant respectively, whereas, Nigella sativa oil was used as a liquid lipid.

Result: The particle size, polydispersity index and zeta potential were found to be 107.4 ± 2.64 nm, 0.25 ± 0.04 and -41.7 mV. The entrapment efficiency and drug content were found to be 70.20% and 89.05% respectively. After intranasal administration of Donepezil hydrochloride (DNZ HCl) loaded NLC's, the maximum concentrations (C_max) of 4.597 µg/mL in brain and 2.2583 µg/mL in blood was achieved after 1 h (T_max).

Conclusion: The formulated DNZ HCl loaded NLCs significantly improved nasal penetration and enhanced drug distribution in brain resulting in a potentially effective intranasal drug delivery system for the effective management of Alzheimer's disease.

Keywords: Alzheimer’s disease; CNS targeting; Donepezil hydrochloride; Nigella sativa oil; high pressure homogenization; intranasal delivery; nano lipid carriers; ultrasonication.