Development and evaluation of intranasal nanostructured lipid carriers encapsulating donepezil HCl and Caesalpinia bonduc seed extract for targeting Alzheimer's disease: in vitro and in vivo evaluation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline. This study aimed to develop and optimise an intranasal nanostructured lipid carrier (NLC) system co-loaded with donepezil (DPZ) hydrochloride and Caesalpinia bonduc seed extract (CBSE) to enhance therapeutic outcomes. LC-MS/MS profiling identified a CBSE bioactive compound with 93.16% structural similarity to neostigmine, suggesting synergistic cholinergic activity. NLCs were prepared using high-pressure homogenisation and ultrasonication, optimised using Design of Experiments (DoEs). The optimised NLCs exhibited an average particle size (PS) of 144.3 ± 1.78 nm, polydispersity index of 0.245 ± 0.025 and a zeta potential of -42.13 ± 2.14 mV, indicating uniformity and stability. Transmission electron microscopy (TEM) confirmed spherical morphology and PS. The formulation showed high entrapment efficiency (67.27 ± 2.32%) with drug loading (16.81 ± 3.59%) and sustained drug release (72.43 ± 4.78%) over 5 h, following zero-order kinetics with super case II transport. Ex vivo nasal permeation studies showed significantly higher permeability (p < 0.05) than control, while histological analysis confirmed nasal mucosal safety. In vivo behavioural studies on AD-induced rats demonstrated significantly improved memory and cognition (p < 0.05) following nasal NLC administration. The DPZ-CBSE NLCs present a promising, safe and non-invasive strategy for effective AD management.